Institute of Biotechnology – Annual report 2009 University of Helsinki

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Institute of Biotechnology – Annual report 2009
University of Helsinki, Viikki Biocenter
Contents
Highlights 2009....................................................... 2
Preface................................................................... 7
Research at the Institute.........................................8
Cell and Molecular Biology..................................8
Hietakangas..........................................................8
Jokitalo................................................................9
Jäntti................................................................. 10
Lappalainen..........................................................11
Rivera.................................................................12
Saarma...............................................................13
Vartiainen........................................................... 14
Ahola..................................................................15
Developmental Biology.......................................16
Jernvall................................................................16
Partanen.............................................................17
Pirvola................................................................18
Shimmi...............................................................19
Thesleff.............................................................. 20
Genome Biology..................................................21
Frilander..............................................................21
Helariutta............................................................22
Holm..................................................................23
Mäkelä............................................................... 24
Schulman............................................................25
Structural Biology & Biophysics......................... 26
Annila................................................................ 26
Bamford..............................................................27
Butcher.............................................................. 28
Goldman............................................................. 29
Heikinheimo........................................................ 30
Iwai....................................................................31
Kalkkinen.............................................................32
Permi.................................................................33
Verkhovsky......................................................... 34
Wikström............................................................35
Core Facilities....................................................... 36
DNA Sequencing and Genomics Laboratory................. 36
Electron Microscopy and CryoEM Unit........................37
Finnish Biological NMR Center................................. 38
Light Microscopy Unit........................................... 39
Protein Chemistry Core Facility................................ 40
Protein Crystallisation Facility.................................. 41
Promoting Careers at the Institute ........................ 42
Careers at BI........................................................ 42
Undergraduate and Master's Programs....................... 42
Graduate training and graduate schools...................... 42
Post-doctoral training............................................ 43
Tenure track........................................................ 43
Graduate and advanced courses . ............................. 44
Viikki Biocenter lectures......................................... 45
Administration...................................................... 46
Board................................................................ 46
Director............................................................. 46
Administration Director.......................................... 46
Scientific Advisory Board........................................ 46
Funding and Human Resources............................... 47
Funding 2009...................................................... 47
Personnel 2009.................................................... 48
Staff members .................................................... 49
Publications...........................................................51
Original articles.....................................................51
Reviews and book chapters......................................55
Other publications.................................................55
PhD theses...........................................................55
Patents and patent applications............................... 56
Institute of Biotechnology
Annual report 2009
Editors: Tomi P. Mäkelä (editor-in-chief),
Arto Halinen, Sanna Leinonen, Minna Oja
Group, group leader and cover photos:
Veikko Somerpuro
The cover picture: Fruit flies (Drosophila melanogaster)
Other photos: Sedeer El-Showk, Wilma Hurskainen,
Eija Jokitalo, Kirsikka Mattila, Eero Roine, Kimmo
Tanhuanpää
Layout: Olli Luotonen
Printing: Vammalan Kirjapaino Oy
Sastamala 2010
Institute of Biotechnology – Annual report 2009
University of Helsinki, Viikki Biocenter
Highlights 2009
January
Irma Thesleff takes position
as acting director of BI
fter a very succesful 18 years at the head of BI, Mart
Saarma steps away from the director position to focus on exciting new leads in research as Academy Professor at BI, and Irma Thesleff starts as acting director for
6 months before new director Tomi Mäkelä starts his 5
year position.
A Jernvall research identified
as a Nature “Evolutionary Gem”
during Darwin’s 200th anniversary
he Jernvall lab investigates mechanisms that guide
evolutionary change resulting in a string of high profile papers during the last years. One of these was selected as one of 15 examples to illustrate the breadth, depth
and power of evolutionary thinking in honor of Darwin’s
200th anniversary. The research uncovered the pattern of
gene expression that governs the development of teeth,
and demonstrates how the pattern of gene expression
can be modified during evolution to produce adaptive
changes in natural systems.
http://www.nature.com/nature/newspdf/evolutiongems.pdf
T May
BI Retreat at Pärnu May 11–12
n extravagant and very successful retreat was arranged
at Pärnu, Estonia with a turnout of 215 and a tightly
packed scientific program.
A February
Meeting down under
ija Jokitalo and Helena Vihinen
(in picture) participated in the 5th
International Meeting of Electron Tomography, which was held for the first
time outside Europe/US in Brisbane
with a good mix of scientists and cutting edge technology. Trip included
also exploration of local fauna and a
seminar by Eija at The Children’s Hospital at Westmead, Sydney.
E Mart Saarma receives prestigious
Lundbeck Foundation Nordic Research
Prize
ong-time BI director and currently Academy
Professor Mart Saarma’s contribution to research into neurotrophic factors was awarded
with the Lundbeck Foundation Nordic Research
Prize. This was only the second time the prize
was awarded to Finland.
L 2 | Institute of Biotechnology
Protein crystallisation services
enhanced
he Protein Crystallisation Unit has
aquired valuable experience using the
Thermo Rhombix crystallization and imaging unit, and arranged a user meeting collecting major European users to Vantaa in
May. Imaging capacity expanded in the
summer with an Exploranova Xtal focus system, which includes a plate hotel, a possibility to schedule imaging, and to share images off site. Further improvements will be
made in 2010 to enhance national services
within Biocenter Finland.
T May
June
Estonian Prime Minister Andrus Ansip visits BI
he prime minister of Estonia Andrus Ansip visited Finland
on invitation by prime minister Matti Vanhanen, and included a visit to BI in his schedule on May 27.
Technology development:
ultra-fast spectrophotometer
eal-time measurements are increasingly important
for advancement of biology. When it comes to
following enzymes and electron transfer in real-time
the challenges are considerable, where the difference is made in microseconds. The Verkhovsky lab
has been able to design a unique ultra-fast spectrophotometer allowing collection of full spectra from
UV to near infrared during unlimited time with the
minimal increment of a single microsecond. This has
allowed for following electron transfer reactions and
intermediate states of the catalytic cycle in the energy transformation cycle carried out by integral
membrane proteins such as cytochrome oxidase on
the mitochondrial membrane, and has already proved
invaluable for the lab.
T R July
Tomi Mäkelä and “Makelab” move to Biocenter 1
very well organized move of the Mäkelä lab took place
first week of July. The lab is located in Biocenter 1 5B,
where the Shimmi lab had kindly made room to move to
Biocenter 3. Also the core facility the lab has been maintaining moved, and developed into the Genome Biology Unit.
Also the director’s office had been renovated thanks to Satu
Sankkila’s efforts during the spring.
http://www.biocenter.helsinki.fi/bi/makela/
http://www.biocenter.helsinki.fi/bi/gbu/
A Site-selective labeling of proteins:
highlighting the middle
esilja Aranko and Hideo Iwai together with colleagues from University of Frankfurt succeeded in ligating 3 domains of the CuracinA protein using split inteins
and protein trans-splicing. This enabled selective labeling
of the central domain for NMR spectroscopy without interference of the other domains. This groundbreaking
protocol may in the future be applied for other site-specific synthetic modifications of proteins such as attaching
fluorophores or even
attachment of polymers for targeting
therapies. Thus the results represent an important technological
advancement in introduction of synthetic
moieties into proteins
even in living cells in
addition to the immediate benefits in investigations of domaindomain interactions in
multi-domain proteins
by NMR.
Angew Chem Int Ed Engl.
2009;48(33):6128-31.
S Annual report 2009 | 3
Highlights 2009
August
July
Neurotrophic factor
MANF shows promise
in preventing neurodegeneration
arkinson’s disease (PD)
is caused by progressive
degeneration of nigrostriatal
dopaminergic neurons, and
current drugs only alleviate symptoms. Neurotrophic
factors might limit degeneration, but so far GDNF
and neurturin have produced
limited benefits, possibly due
to stickiness to extracellular
matrix and poor diffusion in
brain tissue. The Saarma lab
together with colleagues from
the Department of Pharmacy
noted that the recently discovered neurotrophic factor
MANF is better in this regard,
and indeed at least as effective as GDNF in preventing
behavioral symptoms and degeneration of dopaminergic
neurons in a rat model of PD.
J Neurosci. 2009 Jul
29;29(30):9651-9.
P T he mammalian tooth 3D database MorphoBrowser and fossil mammal database
NOW (Neogene of the Old World) maintained by Jernvall lab were transferred to
BI facilitating integration and further development.
morphobrowser.biocenter.helsinki.fi/
http://www.helsinki.fi/science/now/
The Scientific Advisory Board
AB site visit took place August 21–23. From left to right: Dr. Marius Clore, Prof.
John E. Walker, Prof. Kai Simons, Prof. Urban Lendahl, Prof. Jonathan Knowles, Dr.
Pernille Roth.
S Brain Development and Plasticity in Health and Disease, Aug 28
top-quality international scientific symposium took place on August 28 in Biocenter 3 in honor of Mart Saarma’s 60th birthday with presentations by
Andrew Lumsden (King’s College London), Klaus Unsicker
(University of Freiburg), Carlos
September
Ibáñez (Karolinska Institutet,
Stockholm), Liliana Minichiello
New Group Leader Ville Hietakangas starts in improved facilities for
(EMBL Monterotondo), Andres
Drosophila studies
Metspalu (University of Tartu),
ille Hietakangas moved from Steve Cohen’s lab in Singapore, and will focus on
Olle Lindvall (Wallenberg Neuopen questions relating to nutritional sensing in cells and organisms, regulation
roscience Center, Lund), and
of cell growth speed, regulation of fat storage, and insulin resistance mostly using
Ole Petter Ottersen (University
Drosophila as the experimental system. The Hietakangas lab is located in Biocenter 3
of Oslo). The auditorium was
next door to the Shimmi lab, which moved there from Biocenter 1 in June, and set
packed with dignitaries and
up a well-equipped setting for Drosophila studies.
the reception afterward at the
http://www.biocenter.helsinki.fi/bi/hietakangas
University of Helsinki Banquet
http://www.biocenter.helsinki.fi/bi/shimmi/
Hall on Unioninkatu was unforgettable with friends and
colleagues from far and near.
http://www.helsinki.fi/fgsn/
courses/Saarma60.html
V 4 | Institute of Biotechnology
A October
Gorilla comes to Viikki
illu Jaanisoo’s statue ”Anything is possible” came to Viikki Campus
on October. The work is a five-metre high gorilla made out of car
tyres and it sits on a central position in front of the Info Centre.
V DNA sequencing: improved performance
enabling full genome sequencing and
more
he DNA Sequencing and Genomics laboratory upgraded both the Roche 454 next
generation sequencer to Titanium and the AB
SOLiD sequencer to increase both read lengths
and number of reads. This has enabled novel applications like miRNA sequencing and sequencing selected areas of genomes using capture
methodology and comparison of two entire bacterial genomes.
Kankainen et al., PNAS 2009; 106: 17193–17198.
T November
Practical course on protein characterisation
and crystallisation
he three-day practical course organized by Protein
Crystallisation facility was held in November with
four acknowledged international teachers and covering areas from protein purification to membrane protein crystallisation and image analysis. Participants were selected from
applications received from universities around the world.
Juha Partanen appointed Professor of Genetics
at University of Helsinki
hile Juha Partanen had recently taken up a professor position in Turku, the new appointment means his
research efforts will remain on Viikki campus and contribute
to the critical mass in Developmental Biology.
Shinya Matsuda talk at EDRC
iscovering the basis for the highly diversified wing vein
formation in insects by PhD
student Shinya Matsuda from
the Shimmi lab was acknowledged at European Drosophila
Research by selection for an oral
presentation. The result is based
on characterizing how extracellular diffusion of BMP ligands is
regulated for wing vein formation in Drosophila.
http://www.unice.fr/ibdc/EDRC/accueil.htm.
T T D W Critical info for designers of improved enzymes
in biotechnology
ogether with colleagues from Crete, Liege, and New
England Biolabs, the Heikinheimo lab compared structures of three variants of alkaline phosphoatase in complex
with several metal ions, and discovered why the TAB5 and
E. coli APs respond in an opposite way to mutagenesis in
their active sites. The results provide a lesson on chemical
fine tuning and help in efforts to design even more powerful tools for modern biotechnology. The results were published January 2010, in Protein Science.
Annual report 2009 | 5
Highlights 2009
December
Holm publication selected as Fast Breaking Paper
bioinformatics paper authored only by members of
the Holm lab titled “Searching protein structure
databases with DaliLite v.3” was selected as Fast Breaking Paper in the field of Computer Science. The start - a
quote from Lewis Carroll - is hardly conventional: The Red
Queen said, ‘It takes all the running you can do, to keep
in the same place.’ Definitely worth a read! http://www.
sciencewatch.com
A Multiphoton microscope
multiphoton microscope (Leica TCS SP 5 MP SMD
FLIM) was installed in the Light Microscopy Unit
in room 5324. The system has a full set of visible lasers
(405 to 633 nm), a MaiTai HP pulsed infrared TiSa laser, an
upright microscope stand, heating & CO2, 4 spectral imaging detectors, two NDD detectors and a FLIM detector.
Ref: http://www.biocenter.helsinki.fi/bi/lmu/instruments.
htm#MP
A Record number of doctoral theses
total of 21 theses were successfuly defended by
graduate students working at BI (see list of publications):
Bespalov Maxim (Saarma lab)
Euro Liliya (Wikström lab)
Gorbikova Elena (Verkhovsky lab)
Greco Dario (Auvinen lab)
Gupta Rashi (Auvinen lab)
Hultman Jenni (Auvinen lab)
Jaatinen Silja T (Bamford lab)
Kaila Ville RI (Wikström lab)
Kukkaro Petra (Bamford lab)
Leo Jack C (Goldman lab)
Lindholm Päivi (Saarma lab)
Mattila Jaakko (Puig lab)
Nevalainen Elisa (Lappalainen lab)
Oksanen Esko (Goldman lab)
Parkash Vimal (Goldman lab)
Patana Anne-Sisko (Goldman lab)
Pummila Marja (Thesleff lab)
Skwarek-Maruszewska Aneta (Lappalainen lab)
Tselykh Timofey (Mäkelä lab)
Virtanen Heidi (Saarma lab)
Yu Li-Ying (Saarma lab)
A First genome sequenced
in the barley, wheat, and rye group:
keeping slim with retrotransposons
rachypodium distachyon is a new model plant for the
Triticeae cereals barley, wheat, and rye, and was the
first genome to be completed in this important group
within the International Brachypodium Initiative including Alan Schulman. The Schulman lab analyzed the
retrotransposon-driven genome dynamics, and found
that retrotransposons comprise only 21% of the genome,
compared to 26% in rice, 54% in sorghum, and over 80%
in wheat. Although many retrotransposon families are
active, potentially leading to genome size growth, the
genome has been kept small by LTR:LTR recombination.
This process has removed 3 times the current retrotransposon content and at least 6% of the genome. The findings were published February 2010, in Nature.
http://brachypodium.pw.usda.gov/
B Biocenter Finland technology platform grants
groups and core facilities participated successfully in nationally coordinated Biocenter Finland
technology platform applications within BI focus areas
enabling significant development of national services in
2010–12 in the areas of bioinformatics (Liisa Holm, Petri
Auvinen), electron microscopy (Eija Jokitalo and Sarah
Butcher) genome-wide methods (Petri Auvinen ), light microscopy (Maria Vartiainen and Kimmo Tanhuanpää) NMR
(Perttu Permi), protein crystallization (Adrian Goldman
and Pirkko Heikinheimo), proteomics (Nisse Kalkkinen),
and stem cells and biomaterials (Ulla Pirvola).
BI 6 | Institute of Biotechnology
Preface
2009 was a year of festivities and changes at
the Institute of Biotechnology. The Institute –
or BI – celebrated its 20th anniversary with a fantastic retreat and symposium held in Pärnu May 11–12 for the entire
staff. During a reception arranged in honor of Mart Saarma
receiving the prestigious Lundbeck prize, rector Thomas Wilhelmsson crystallized what the University of Helsinki thinks of
its 20 years investment today: “BI is one the crown jewels of
the University of Helsinki”. This was a well deserved acknowledgement of the accomplishements of the Institute under the
direction of Mart Saarma. The festivities ended in the Annual
Christmas Party, where a very different kind of treat was provided by our IT coordinator Atro Tossavainen: his outstanding
energetic and vital drag performance awed and inspired us all.
One of the big changes occurred on the very first day of
the year, where Mart Saarma was found pipetting happily at
the lab bench instead of the director's office. Irma Thesleff
looked after the Institute’s interests successfully during the
spring when decisions were prepared on the structures of the
University of Helsinki under the new Universities Act where
universities are independent judicial bodies with significantly
more freedom and responsibility. With these excellent preparations it was easy to get started in my new job in July fully
realizing that I was stepping into very big boots. Together
with help from the Scientific Advisory Board and the Institute Board with its new chairman Esko Ukkonen we generated a new strategic plan for the Institute with a vision to
strengthen the position of the Institute as an international
outstanding research institute in biosciences profiled through
high impact research and renowned scientists.
A major factor in the success of the Finnish biosciences
has been the longstanding strategic biotechnology funding
from the Ministry of Education from 1990–2006. One of the
achievements was Biocenter Finland, a structure coordinating
activities and infrastructures within the six national biocenters
and chaired by Taina Pihlajaniemi and Mart Saarma since 2007.
Bioscience is one of very few areas nationally where such coordination has been successful, and this was acknowledged by
the Ministry of Education this year: it gave Biocenter Finland
responsibility and significant resources for restructuring biosciences in Finland during 2010–12. There was a tremendous
effort at the grassroots level during the year to organize the
restructuring with a major focus on national technology platforms. The coming three years are a opportunity for us and
the entire Biocenter Finland – under the new director Eero
Vuorio – to stand up to the restructuring challenge and thereby take Finnish bioscience technologies to the next level.
In August, an evaluation of the Institute was performed
by the Scientific Advisory Board. In addition to the program
presentations and interviews chaired by Jonathan Knowles
an active panel discussion on the “next wave in biology” was
moderated by Kai Simons. The report was very positive indicating that the Institute remains a major centre of scientific
and technological excellence, continues to have an excellent
publication record internationally, and has been successful in
recruiting talented scientists from outside Finland. The success was considered to be based on rigorous focus on scientific excellence, strong leadership, flexible administrative structure, and continued investement into world class molecular
technologies. The SAB visit also led to clarification of group
leader positions at the Institute with formulation of a threetier tenure track for new group leaders to form a pilot at the
University of Helsinki. Amongst all these festivities and changes the BI staff
reached record-breaking achievements in scientific output
as well as in graduate and undergraduate education and the
administration coped admirably with occasionally chaotic
circumstances. With this enthusiastic spirit we are perfectly
positioned to take on new opportunities, and develop the Institute as an international, competitive and rewarding workplace.
Tomi P. Mäkelä
Director
Research at the Institute
Cell and Molecular Biology
Signaling in growth and metabolism
 Inter-
and intracellular signaling on nutritional status
focusing on insulin/IGF signaling in Drosophila
A nimals monitor constantly their nutritional status. They use this information to adjust important physiological processes, such as tissue growth and metabolic reactions. Our lab is interested in understanding, how animals perceive their
nutritional status and how this information is mediated between different types of
cells as well as within the cell. Our main focus is to understand the regulation and
physiological consequences of insulin/IGF signaling (IIS), which is the main humoral
response to nutrients in multicellular animals.
The nutrient-regulated signaling mechanisms and pathway components currently
known are well conserved. Our main model system is the fruit fly Drosophila melanogaster, which offers several advantages for research on this topic. Among these
are low genetic redundancy, a versatile genetic toolkit for tissue-specific loss- and
gain-of-function analyses as well as multitude of assays to monitor the metabolic
status and growth of the animal. In parallel, we are using mammalian tissue culture
models to test the conservation of our findings and assess their relevance to human
metabolic diseases.
At the moment we are performing genetic screens, both in vivo and in cell culture. These screens are expected to identify upstream and downstream regulators
of IIS. We are also analyzing phenotypes of novel mutants involved in carbohydrate
metabolism, aiming to reveal their physiological functions and testing their involvement in IIS and other established metabolic signaling networks.
Selected publications
Hietakangas V, Cohen SM. Regulation of tissue growth through nutrient sensing. Annu. Rev.
Genet. 2009; 43: 389−410.
Szuplewski S, Sandmann T, Hietakangas V, Cohen SM. Drosophila Minus is required for cell
proliferation and influences Cyclin E turnover. Genes Dev. 2009; 23: 1998−2003.
Teleman AA*, Hietakangas V*, Sayadian AC, Cohen SM. Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell Metab. 2008; 7: 21−32.
Hietakangas V, Cohen SM. Re-evaluating AKT regulation: role of TOR complex 2 in tissue
growth. Genes Dev. 2007; 21: 632−637.
Hietakangas V*, Anckar J*, Blomster HA, Fujimoto M, Palvimo JJ, Nakai A, Sistonen L. PDSM,
a motif for phosphorylation-dependent SUMO modification. PNAS. 2006; 103: 45−50.
* equal contribution
8 | Institute of Biotechnology
PI Ville Hietakangas
BI Group Leader since 2009
PhD 2004, University of Turku, Finland
Post-doctoral research at EMBL
Heidelberg, Germany, 2005−2007 and
at Temasek Life Sciences Laboratory,
Singapore, 2007−2009
Academy Research Fellow,
Academy of Finland, since 2009
http://www.biocenter.helsinki.fi/bi/
hietakangas
Email: ville.hietakangas@helsinki.fi
Group members
Post-doctoral fellow: Jaakko Mattila
Graduate students: Kiran Hasygar,
Essi Lind
Morphological determinants
of the endoplasmic reticulum
 ER
network organization changes during the cell division
and regulators of the ER morphology
T he endoplasmic reticulum (ER) is highly dynamic and complex organelle
that hosts fundamental cellular functions such as the synthesis, modification
and transport of secretory and membrane proteins and many lipids. ER also has a
central role in cell fate decisions as many cell death responses are initiated there.
We are studying the sub-compartmental organization and morphogenesis of the ER
in mammalian cells. Our main questions are how ER network organization changes
during the cell division and what are the regulators of the ER morphology.
Morphologically ER is composed of two very different forms, flattened sheets
and tubules which branch to generate a polygonal network. Sheets are predominant
over tubules in the central area of the cell, whereas peripheral areas close to the
plasma membrane have long interconnected tubules (Puhka et al., 2007). Our quantitative confocal and EM analyses show that the ER undergoes dramatic reorganization during cell division in cultured mammalian cells as mitotic ER profiles become
shorter and more branched. 3D modeling by electron tomography reveals that the
abundant interphase structures, sheets, are lost and subsequently transform into a
branched tubular network that remains continuous.
We provide mechanistic insight into the inheritance of the ER by showing that
similar changes in the ER structure are induced by stripping of ribosomes with puromycin from the interphase ER. This is consistent with the observed loss of ribosomes
normally occurring during mitosis. Thus we propose that the structural changes in
mitotic ER are linked to ribosomal action on the ER membranes.
Our aim now is to study further the maintenance of sheet structures and the
transition of ER sheets into tubular network by focusing on the molecular determinants supporting these structures. Our second aim is to examine systematically the
role of cytoskeleton in the maintenance and dynamics of the ER morphology.
PI Eija Jokitalo
PhD 1996, University of Helsinki, Finland
Postdoctoral research at Imperial Cancer
Research Fund, Cell Biology Laboratory,
London, UK, 1997–1999
Researcher at the Institute, 2000–2001
www.biocenter.helsinki.fi/bi/em
Email: eija.jokitalo@helsinki.fi
Group members
Senior scientist: Helena Vihinen
Graduate students: Merja Joensuu,
Maija Puhka, Olli Rämö
Technicians:
Virpi Himanen (until 7.9.2009),
Pirkko Leikas-Lazanyi (until 31.8.2009),
Mervi Lindman,
Antti Salminen (since 1.10.2009),
Arja Strandell
Undergraduate student: Giuseppa Piras
Ylä-Anttila P*, Vihinen H*, Jokitalo E, Eskelinen E-L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 2009; 5: 1180−1185.
Jansen M, Pietiäinen VM, Pölönen H, Rasilainen L, Koivusalo M, Ruotsalainen U, Jokitalo E,
Ikonen E. Cholesterol substitution increases the structural heterogeneity of caveolae. J. Biol.
Chem. 2008; 283:4610−4618.
Puhka M, Vihinen H, Joensuu M, Jokitalo E. ER remains continuous and undergoes sheet
to tubule transformation during cell division in mammalian cells. J. Cell Biol. 2007;
179:895−909.
Mattila PK, Pykäläinen A, Saarikangas J, Paavilainen VO, Vihinen H, Jokitalo E, Lappalainen P.
Missing-In-Metastasis (MIM) and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR
domain like mechanism. J. Cell Biol. 2007; 176:953−64.
Uchiyama K*, Totsukawa G*, Puhka M*, Kaneko Y, Jokitalo E, Dreveny I, Beuron F, Zhang X,
Freemont P and Kondo H. p37 is a p97 Adaptor required for golgi and ER biogenesis in interphase and at the end of mitosis. Dev. Cell 2006; 11:803–816.
* equal contribution
Research at the Institute | Cell and Molecular Biology
Cell polarity regulation
in differentiation and development
 Genes, proteins, and
interactions regulating cell polarity and
exocyst complex function in budding yeast and nematodes
C orrect cellular polarity is a prerequisite for differentiation and development in uni- and multicellular organisms. Polarity generation is intimately linked
with molecular machineries that govern transport and targeting of intracellular proteins at the cell surface. Cell migration is a cell polarity-dependent process and while
essential for organism development, when uncontrolled, cell migration can drive
metastasis formation, the major cause of death in cancer patients.
Our previous studies have linked several genes and proteins with the central
eukaryotic cell polarity regulator, the exocyst complex. These interactions are conserved in evolution and we have investigated their functional role using both yeast
S. cerevisiae and the nematode C. elegans as model systems. Our recent results include demonstration that only the trans-membrane domain of yeast Sec61ß is sufficient for its in vivo function and that this protein has interaction partners outside
protein translocation machinery (Feng et al., 2007, Zhao and Jäntti, 2009). We have
shown how Mso1p interacts with Sec1p in cell polarity and differentiation (Knop et
al., 2005). Using yeast as a model, we have characterized the consequences of tumor predisposing mutations for fumarase enzyme function (Kokko et al., 2006) and
have investigated the possible contribution of BRCA2 and exocyst subunit interacting DSS1 for breast cancer predisposition (Syrjäkoski et al., 2007). In addition, we
have established the use of C. elegans as a metazoan model organism and characterized the role of the exocyst interacting dss-1 gene in animal development (Pispa et
al 2008). Our current projects focus on elucidation of cell polarity regulation and exocyst complex function. We are presently identifying novel genes and proteins participating in polarity regulation, investigating the molecular interactions the exocyst
complex displays and how these interactions contribute to cell polarity regulation.
Zhao X, Jäntti J. Functional characterization of the trans-membrane domain interactions of
the Sec61 protein translocation complex beta-subunit. BMC Cell Biol. 2009; 10: 76.
Pispa J, Palmen S, Holmberg CI, Jäntti J. C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth. BMC Dev Biol. 2008; 8: 51.
Feng D, Zhao X, Soromani C, Toikkanen J, Römisch K, Keränen S, Jäntti J. The trans-membrane
domain is sufficient for Sbh1p function and it mediates interactions with Sec61-translocon
and Rtn1p. J. Biol. Chem. 2007; 282: 30618–30628.
Heikkinen-Poussu E, Jäntti J, Savilahti H. A gene truncation strategy generating N- and Cterminal deletion variants of proteins for functional studies: Mapping of the Sec1p binding
domain in yeast Mso1p by a Mu in vitro transposition-based approach. Nucleic Acid Res.
2005; 8: 33(12), e104.
Knop MK, Miller J, Mazza M, Feng D, Weber M, Keränen S, Jäntti J. Molecular interactions position Mso1p, a novel PTB domain homologue, in the interface of the Exocyst complex and
the exocytic SNARE machinery. Mol. Biol. Cell. 2005; 16: 4543–4556.
PI Jussi Jäntti
Postdoctoral research VTT Technical
Research Center of Finland, 1995–1999;
Cambridge Institute of Medical Research,
University of Cambridge UK, 1999
Docent 2002, University of Helsinki,
Finland
Group Leader at VTT Technical Research
Center of Finland 2001–2005
www.biocenter.helsinki.fi/bi/jantti
Email: jussi.jantti@helsinki.fi
Group members
Postdoctoral fellows: Nina Aro,
Johanna Pispa, Konstantin Chernov
Graduate students: Marion Weber,
Qiang Yuan
Technician: Anna-Liisa Nyfors (half-time)
Regulation of actin and plasma
membrane dynamics in mammalian cells
 Roles
of actin binding proteins in the dynamics of contractile
and protrusive actin filament structures
 Regulation of the actin cytoskeleton – plasma membrane interplay
in cell motility and morphogenesis
C oordinated polymerization of actin filaments against cellular membranes
provides the force for a number of biological processes, including cell morphogenesis, motility, endocytosis, and phagocytosis. In addition, actin filaments together with myosin filaments form contractile structures in muscle and non-muscle cells.
Thus, the actin cytoskeleton has a fundamental role in a large number of physiological processes in all eukaryotes. Furthermore, abnormalities in actin-dependent processes, including cell motility and cytokinesis, often occur in cancer cells and many
pathogens exploit the actin polymerization machinery of the host cell during the
infection process. Thus, elucidating the mechanisms of actin dynamics will also be
valuable for understanding these actin-dependent pathological states.
Our laboratory applies a wide range of biochemical, cell biological, and genetic
methods to reveal how the structure and dynamics of the actin cytoskeleton are
regulated during various cellular and developmental processes. One of our main interests is to examine the roles of actin monomer binding proteins twinfilin and
cyclase-associated-protein (CAP) in actin dynamics and to elucidate how these proteins contribute to various motile processes in cells. We also study how assembly
and dynamics of contractile actin filament structures in muscle cells (myofibrils) and
non-muscle cells (stress fibers) are regulated by different actin binding proteins, and
how the actin cytoskeleton contributes to inducible secretion in mast cells. Finally,
we aim to reveal how membrane phospholipids regulate actin dynamics, and how
the I-BAR domain family proteins deform PI(4,5)P2-rich membranes to coordinate
actin and plasma membrane dynamics during cell motility and morphogenesis.
PI Pekka Lappalainen
Research Director of Cell and Molecular
Biology Program since 2004
PhD 1995, EMBL-Heidelberg, Germany
Post-doctoral research at University of
California, Berkeley, USA 1995–1998
EMBO Young Investigator Programme
(EMBO YIP) Award, 2001
www.biocenter.helsinki.fi/bi/Lappalainen
Email: pekka.lappalainen@helsinki.fi
Group members
Post-doctoral fellows: Elena Kremneva,
Martina Serlachius, Sari Tojkander,
Hongxia Zhao
Graduate students: Gergana Gateva,
Anette Pykäläinen, Juha Saarikangas,
Maarit Sihvo, Aneta Skwarek-Maruszewska
Technician: Anna-Liisa Nyfors (half-time)
Hotulainen P, Llano O, Smirnov S, Tanhuanpää K, Faix J, Rivera C, Lappalainen P. Defining
mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J. Cell Biol.2009; 185: 323−339.
Saarikangas J, Zhao H, Pykäläinen A, Laurinmäki P, Mattila PK, Kinnunen P, Butcher SJ, Lappalainen P. Molecular mechanisms of membrane deformation by I-BAR domain proteins. Curr.
Biol. 2009; 19: 95−107.
Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat. Rev.
Mol. Cell Biol. 2008; 9: 446−454.
Paavilainen VO, Oksanen E, Goldman A, Lappalainen P. Structure of the actin-depolymerizing
factor homology domain in complex with actin. J Cell Biol. 2008; 182: 51−59.
Chereau D, Boczkowska M, Skwarek-Maruszewska A, Fujiwara I, Hayes DB, Renowski G, Lappalainen P, Pollard TD, Dominguez R. Leiomodin is an actin filament nucleator in muscle cells.
Science. 2008; 320: 239−243.
Research at the Institute | Cell and Molecular Biology
Role of ion transporters in neurotransmission
 KCC2
as a factor synchronizing inhibitory and excitatory
synapses and their maturation
 Interplay between intracellular chloride regulation
and neurotrophic factors in epilepsy and survival by thyroxin
A
central question in neurobiology is the elucidation of the molecular
mechanisms orchestrating synaptic maturation in the central nervous system.
Alterations in the mechanisms synchronizing inhibitory and excitatory synapses and
their maturation may lead to developmentally related disorders including autism,
mental retardation and epilepsy. Despite the essential importance of these events
very little is known about the molecular mechanisms involved.
Our recent data identified the neuron specific K-Cl cotransporter KCC2 as a potential synchronizing factor. We showed previously that this transporter plays a
pivotal role in the maturation of inhibitory synapses. Its developmental activation
induces a decrease in intracellular chloride that sets the gradual shift in GABA/glycine-mediated responses from depolarizing to hyperpolarizing. Now we have found
that KCC2 also plays a crucial role in the formation of dendritic spines as well as
functional glutamatergic synapses. Strikingly, this is independent of the chloride extrusion activity of KCC2 and relies on the interaction of the intracellular domain
with spine proteins e.g. 4.1N that directly link it to the regulation of the dendritic
spine cytoskeleton.
Because neurotrophic factors are regulated by neuronal activity and can regulate inhibitory and excitatory synapses, they are key molecules to mediate developmental and adult forms of synaptic plasticity. We have elucidated part of the
mechanisms involved in the interplay between intracellular chloride regulation and
neurotrophic factors in clinically important paradigms for epilepsy and CNS injury.
Furthermore, our recent results demonstrate that the survival promoting effect of
the developmentally important hormone Thyroxin is dependent on the interplay between trophic factors and chloride regulation. In the future we will dissect in detail
the molecular network connecting KCC2 with the cytoskeleton and its importance
for the maturation processes of both glutamatergic and GABAergic synapses. Also
the interplay between trophic factors and KCC2 mediated regulation of the structural morphological dynamics of dendritic spines and its impact on synaptic plasticity will be investigated.
Selected publications:
mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol. 2009; 185(2): 323–39.
Shulga A, Blaesse A, Kysenius K, Huttunen HJ, Tanhuanpää K, Saarma M, Rivera C. Thyroxin
regulates BDNFshok expression to promote survival of injured neurons. Mol Cell Neurosci.
2009; 42(4): 408–18.
Shulga A, Thomas-Crusells J, Sigl T, Blaesse A, Mestres P, Meyer M, Yan Q, Kaila K, Saarma M,
Rivera C, Giehl KM. Posttraumatic GABA(A)-mediated [Ca2+]i increase is essential for the induction of brain-derived neurotrophic factor-dependent survival of mature central neurons. J
Neurosci. 2008; 28(27): 6996–7005.
Huberfeld G, Wittner L, Clemenceau S, Baulac M, Kaila K, Miles R, Rivera C. Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J Neurosci. 2007;
27(37): 9866–73.
Li H, Khirug S, Cai C, Ludwig A, Blaesse P, Kolikova J, Afzalov R, Coleman SK, Lauri S, Airaksinen MS, Keinänen K, Khiroug L, Saarma M, Kaila K, Rivera C. KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron. 2007; 56(6): 1019–33.
PI Claudio Rivera
PhD 1995, Stockholm University, Sweden
Postdoctoral Fellow of the Swedish Natural Science Research Council performed
at the Department of Animal Physiology
University of Helsinki, 1996–1998
Docent in Neurobiology, University of
Helsinki 2002
Project Leader at the Institute 2002–
2007
www.biocenter.helsinki.fi/bi/rivera
Email: claudio.rivera@helsinki.fi
Group members
Senior scientist: Sergei Smirnov
Postdoctoral fellow: Anastasia Ludwig
Graduate students: Anastasia Shulga,
Olaya Llano, Ana Cathia Magalhaes,
Pepin Marshal
Technician: Miika Palviainen
Undergraduate students: Shetal Soni,
Tero Rosenqvist
The group is a member of Academy
of Finland Centre of Excellence in
Molecular and Interactive Neuroscience Research
http://www.biocenter.helsinki.fi/
neurocoe/index.htm
Structure, biology and therapeutic potential
of neurotrophic factors
 GDNF
family ligands and their receptors in development,
cell death, and neurodegeneration of midbrain dopaminergic neurons
 Receptors, intracellular signaling and anti-apoptotic effects of
MANF and CDNF
O ur group is interested in the structure, biology and therapeutic effects
of neurotrophic factors. We study GDNF family ligands (GDNF, neurturin, artemin and persephin) and their receptors, GFRa1–4 and Ret. We investigate the
structure of GDNF family ligands and their complexes with receptors but also search
for new receptors for these ligands. To study the role of GDNF family ligands and
their receptors in normal development, cell death and neurodegeneration of the
midbrain dopaminergic neurons, we have developed mice enabling conditional deletion of GDNF and GFRa1 from different regions of the nervous system. We have also
developed mice over-expressing GDNF from its own locus and found that developmental effects of GDNF are much broader than earlier understood.
Our group has discovered a new neurotrophic factor called cerebral dopamine
neurotrophic factor (CDNF) that, together with mesencephalic astrocyte-derived
neurotrophic factor (MANF) constitute a novel family of neurotrophic factors. We
are currently studying the structure, biology and therapeutic potential of these new
factors. We have solved the crystal structure of CDNF and MANF and found that
they structurally form a new class of proteins. We try to identify the receptors,
intracellular signaling and anti-apoptotic effects of MANF and CDNF that according
to our results occurs via a completely novel mechanism. We tackle these problems
by combining structural biology, apoptotic and electrophysiological approaches. To
study the basic function we have developed conventional and conditional knockout
mice of CDNF. Interestingly, CDNF knockout mice have a lethal phenotype in the
very early development. Since CDNF and MANF are most potent neurorestorative
proteins in rodent models of Parkinson’s disease they are, together with GDNF, extremely attractive therapeutic candidates. We are currently making serious efforts
to take CDNF to Phase I clinical trials for the treatment of Parkinson’s disease.
Palgi M, Lindström R, Peränen J, Piepponen TP, Saarma M, Heino TI. Evidence that DmMANF
is an invertebrate neurotrophic factor supporting dopaminergic neurons. PNAS. 2009 Feb
17;106(7): 2429–2434.
Voutilainen MH, Bäck S, Pörsti E, Toppinen L, Lindgren L, Lindholm P, Peränen J, Saarma M*,
Tuominen RK. Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat
model of Parkinson’s disease. J Neurosci. 2009; 29(30): 9651–9. *Corresponding author
Parkash V, Leppänen V-M, Virtanen H, Jurvansuu JM, Bespalov MM, Sidorova YA, RunebergRoos P, Saarma M, Goldman A. The Structure of the glial cell line-derived neurotrophic factorcoreceptor complex. Insights into RET signalling and heparin binding. J. Biol. Chem. 2008;
283(50): 35164–35172.
Yu LY, Saarma M, Arumäe U. Death receptors and caspases but not mitochondria are activated in the GDNF- or BDNF-deprived dopaminergic neurons. J Neurosci. 2008; 28: 7467–7475.
Lindholm P, Voutilainen MH, Laurén J, Peränen J, Leppänen V-M, Andressoo J-O, Lindahl M,
Janhunen S, Kalkkinen N, Timmusk T, Tuominen RK, Saarma M. Novel neurotrophic factor
CDNF protects and rescues midbrain dopamine neurons in vivo. Nature. 2007; 448: 73–77.
PI Mart Saarma
BI Group Leader since 1990,
Director of BI, 1990–2008
Academy Professor, 2009
PhD 1975, University of Tartu, Estonia
Postdoctoral research at the Moscow
Institute of Molecular Biology, Russia,
1975; Friedrich Miescher Institute, Basel,
Switzerland, 1982
Head of the Department of Molecular
Genetics, Estonian Academy of Science,
1980–1990
Director of the Centre of Excellence in
Molecular and Integrative Neuroscience
Research, 2008
EMBO member, 2005
Academician of the Estonian Academy
of Sciences, 1990
www.biocenter.helsinki.fi/bi/saarma
Email: mart.saarma@helsinki.fi
Group members
Senior scientists: Johan Peränen,
Pia Runeberg-Roos
Postdoctoral fellows: Jaan-Olle Andressoo, Jukka Kallijärvi, Maria Lindahl, Päivi
Lindholm, Liina Lonka, Yulia Sidorova
Graduate students: Carolina Amberg,
Maxim Bespalov, Ave Eesmaa,
Maria Lume, Anmol Kumar, Erik Palm,
Satu Leppänen, Heidi Virtanen
Technicians: Hanna-Mari Heikkinen,
Satu Åkerberg, Susanna Wiss, Elisa
Piranen
Subgroup of Urmas Arumäe, PhD
Postdoctoral fellow: Li-ying Yu
Graduate students: Maili Jakobson,
Kert Mätlik
Molecular and Interactive Neuroscience Research
http://www.biocenter.helsinki.fi/
neurocoe/index.htm
Actin as an organizer of gene expression
 Mechanisms
of nucleocytoplasmic shuttling and polymerization
of nuclear actin
 Roles of novel nuclear actin regulating proteins
in actin-regulated gene expression
T he actin cytoskeleton has an essential role in several important cell biological processes, including cell motility and membrane dynamics. These cytoplasmic functions of actin are well characterized, but the role of actin in the nucleus
has been less obvious. Recent studies have, however, identified actin as an essential
component of several nuclear complexes, including basal transcription machinery
and chromatin remodelers. Moreover, nuclear actin can also function as a signal
responsive regulator of specific transcription factors. Nuclear actin levels respond to
cellular stress, and may therefore play a role in the pathology of different diseases.
Hence the functions of actin in the nucleus seem to be as versatile, and as important, as in the cytoplasm. However, the molecular mechanism by which actin functions in the nucleus has remained largely unclear.
To understand how actin is able to contribute to essential nuclear processes our
lab is studying several aspects of actin within the nuclear compartment. We are developing several microscopy-based tools to visualize nuclear actin. We are, for example, using live-cell imaging to study nucleocytoplasmic shuttling and polymerization
properties of nuclear actin. We have recently shown that the nuclear import of actin occurs by an energy-dependent mechanism, and have identified candidate proteins for mediating this process. Moreover, by using RNAi-based screening, we have
discovered novel nuclear actin regulating proteins, and are currently elucidating in
molecular detail how they impinge on actin. Two of the most interesting factors are
Fbp11, which may function as a general regulator of nuclear actin polymerization,
and Phactr-protein family, which seem to sense cellular actin levels to modulate cell
morphology. In the future, we aim to apply the knowledge that we have gained
from the basic properties of nuclear actin to elucidate the molecular mechanisms by
which actin regulates gene expression.
Guettler S, Vartiainen MK, Miralles F, Larijani B, Treisman R. RPEL motifs link MAL but not
myocardin to Rho signaling via actin binding. Mol Cell Biol. 2008; 28(2): 732−742.
Vartiainen MK. Nuclear actin – from form to function. FEBS Letters. 2008; 582(14):
2033−40.
Vartiainen MK, Guettler S, Larijani B, Treisman R. Nuclear actin regulates dynamic subcellular
localization and activity of the SRF cofactor MAL. Science. 2007; 316 (5832): 1749−52.
Vartiainen MK, Machesky LM. The WASP-Arp2/3 pathway: genetic insights. Curr Opin Cell
Biol. 2004; 16(2): 174−81.
PI Maria Vartiainen
Postdoctoral research at University of
Birmingham, UK 2003; Cancer Research
UK, London, UK 2003–2007
www.biocenter.helsinki.fi/bi/vartiainen
Email: maria.vartiainen@helsinki.fi
Group members
Postdoctoral fellow: Guillaume Huet
Graduate students: Joseph Dopie,
Kari-Pekka Skarp
Undergraduate students: Kaisa Rajakylä,
Johanna Puusaari
RNA virus replication and its inhibition
 Formation, structure, function, and
intracellular dynamics
of the membrane-associated alphavirus replication complexes
 Development of screening assays, and screening for inhibitors
of RNA virus replication
R NA viruses cause devastating infectious diseases, and new epidemics continue to emerge. We aim towards deep understanding of RNA virus replication
at the molecular level. Through the discovery of basic mechanistic principles, we
also hope to develop new and general antiviral strategies. We mainly work with
alphaviruses, including Semliki Forest virus. The mosquito-borne alphaviruses can
cause large outbreaks, as exemplified by the recent Chikungunya virus epidemic.
The replication of all positive-strand RNA viruses takes place in membrane-associated complexes in the cytoplasm of infected cells. The membrane probably plays
organizing and supporting, as well as protecting and activating roles for the replication complex. The replication complex of alphaviruses and many related viruses is
a membrane invagination of 50 nm in diameter. We have shown by electron microscopic tomography that each invagination is connected to the cytoplasm by a
narrow neck structure. Thousands of active replication complexes are found on the
inner surface of the plasma membrane and on the outer surface of endo-lysosomal
vacuoles. The structure and formation of the replication complexes are studied by
advanced electron microscopy and confocal microscopy methods.
We investigate the individual functional domains of the RNA replicase. For the alphavirus protease, we have discovered novel modulation by RNA, and for the macro
domain, which is also present in several cellular proteins, we have characterized its
interaction with ADP-ribose derivatives. We also study other viruses, including hepatitis E virus and the infamous SARS coronavirus, for which we have discovered one
of the RNA capping enzymes. In antiviral studies, we have developed automated
screening methods utilizing marker genes inserted in the alphavirus genome. We
have discovered antivirally active compounds, whose molecular mechanism of action
is an interesting question.
Tero Ahola
Coordinator of Biocenter Finland
since 2008
Wisconsin-Madison & Howard Hughes
Medical Institute, USA and Pfizer Global
Research & Development, Sandwich, UK,
1998–2001
Academy Fellow at the Institute
2002–2007
www.biocenter.helsinki.fi/bi/animalvirus
Email: tero.ahola@helsinki.fi
Group members
Postdoctoral fellow: Kirsi Hellström
Graduate students: Giuseppe Balistreri,
Maarit Neuvonen, Leena Pohjala,
Pirjo Spuul
Chen Y, Cai H, Pan J, Xian N, Tien P, Ahola T, Deyin G. Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. PNAS. 2009; 106:
3484−3489.
Neuvonen M, Ahola T. Differential activities of cellular and viral macro domain proteins in
binding of ADP-ribose metabolites. J. Mol. Biol. 2009; 385: 212−225.
Pohjala L, Alakurtti S, Ahola T, Yli-Kauhaluoma J, Tammela P. Betulin-derived compounds as
inhibitors of alphavirus replication. J. Nat. Prod. 2009; 72: 1917−1926.
Balistreri G, Caldentey J, Kääriäinen L, Ahola T. Enzymatic defects of the nsP2-proteins of
Semliki Forest virus temperature-sensitive mutants. J. Virol. 2007; 81: 2849−2860.
Spuul P, Salonen A, Merits A, Jokitalo E, Kääriäinen L, Ahola T. Role of the amphipathic membrane binding peptide of Semliki Forest virus replicase protein nsP1 in membrane association
and virus replication. J. Virol. 2007; 81: 872−883.
Developmental Biology
Evolution and development
 Predicting evolution through development
 Understanding tooth senescence using lemurs
as a model
E volutionary developmental biology is a field of biology aiming to uncover
how developmental mechanisms and genes have changed in the evolution of
phenotypes. Our aim is to construct developmental-based models that are used to
predict patterns of phenotypic variation. Our ultimate goal is to discover the logic’
that governs the production of the phenotypic variation available for natural selection. Most of our work uses mammalian dentition as a model system in the context
of both micro- and macroevolution, and methods ranging from developmental biology experiments to computer models simulating development. Our developmental
biology questions include regulation of tooth shape, number, and regeneration.
Tooth phenotypes are invariably complex and difficult to fully characterize, and
we are developing approaches to allow fast-throughput analysis of three-dimensional
shapes. To study natural and mutant phenotypes, we have developed a computerized MorphoBrowser database for three-dimensional phenotypes. MorphoBrowser allows the linking of macroevolution level collections on fossils, microevolution level
data collected from natural populations, and experimentally changed morphologies
of mouse mutants (morphobrowser.biocenter.helsinki.fi/).
Another aim is to understand factors that have contributed to the evolution of
longevity in the wild. Dental development is one measure that has been used extensively to estimate maturation rates and ages in mammals, especially in primates.
We extend these studies by measuring life-long changes in the structural design of
the teeth (dental senescence). The objective is to discover what it means to get old
in the smallest-bodied primates, mouse lemurs, in a wild rainforest setting in Madagascar. The tiny 45 gram (1.6 oz) mouse lemurs, which in captivity can live almost
ten times longer than mice, bridge work to the biological basis of long lifespan and
senescence in humans.
Munne PM, Tummers M, Järvinen E, Thesleff I, Jernvall J. Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction. Development. 2009; 136: 393−402.
Plyusnin I, Evans AR, Karme A, Gionis A, Jernvall J. Automated 3D phenotype analysis using
data mining. PLoS ONE. 2008; 3(3): e1742. doi:10. 1371/journal.pone.0001742.
Evans AR, Wilson GP, Fortelius M, Jernvall J. High-level similarity of dentitions in carnivorans
and rodents. Nature. 2007; 445: 78−81.
Kavanagh KD, Evans AR, Jernvall J. Predicting evolutionary patterns of mammalian teeth from
development. Nature. 2007; 449: 427−432.
Kassai Y, Munne P, Hotta Y, Penttilä E, Kavanagh K, Ohbayashi N, Takada S, Thesleff I, Jernvall
J, Itoh N. Regulation of mammalian tooth cusp patterning by ectodin. Science. 2005; 309:
2067−2070.
King SJ, Arrigo-Nelson SJ, Pochron ST, Semprebon GM, Godfrey LR, Wright PC, Jernvall J.
Dental senescence in a long-lived primate links infant survival to rainfall. PNAS. 2005; 102:
16579−16583.
PI Jukka Jernvall
Postdoctoral research at Stony Brook
University, NY, USA, 1996−1997; at
University of Helsinki 1997−2000
Professor, Evolutionary and Developmental Biology, 2005−2009
Academy Professor 2010
www.biocenter.helsinki.fi/bi/evodevo
Email: jukka.jernvall@helsinki.fi
Group members
Postdoctoral fellows: Ian Corfe,
Elodié Renvoisé
Graduate students: Pauliina Munne,
Enni Harjunmaa, Sarah Zohdy
Technicians: Susanna Sova, Raija Savo
lainen (jointly with Irma Thesleff)
Undegraduate student: Tuomas Kankaanpää
Regulation of neuronal development
in the embryonic brain
 Differentiation and proliferation of neuronal precursors
 Intercellular growth factor signals and cell-type specific
transcription factors control development
W e are interested in the processes which control proliferation and differentiation of neural progenitor cells in the developing vertebrate brain, especially the mid- and hindbrain. Among other neuronal types, the embryonic midbrain
gives rise to the dopaminergic neurons, which are important for regulation of motor
activity and adjustment of the behavioural state of an individual. Degeneration of
some of the midbrain dopaminergic nuclei has been associated with the movement
disorder Parkinson’s disease. Also psychiatric disease like addiction, depression and
schizophrenia are thought to be caused by alterations in the activity of neural circuitries in the midbrain and anterior hindbrain.
Our focus has been on investigating how intercellular growth factor signals and
cell-type specific transcription factors control development of the specific neuronal
populations in the embryonic mid- and hindbrain. We have characterized how fibroblast growth factor (FGF) signals from the isthmic organizer, a key regulatory signaling center, are received by their target cells in the mid- and hindbrain. We have
also shown how FGF signalling regulates cell survival, regionalization, proliferative
neural stem cell identity and maturation of dopaminergic neuron precursors. The
activity of the dopaminergic neurons is controlled by other neurons in the midbrain,
including different inhibitory GABAergic neuron subpopulations. We have identified
transcription factors acting as essential selectors of the inhibitory GABAergic vs.
excitatory glutamatergic fate in the post-mitotic midbrain precursor cells. This work
has also revealed unexpected heterogeneity in the developmental origins and regulatory mechanisms of the midbrain GABAergic neurons.
Our current work is focused on the maintenance of neural stem cell properties
and transcriptional regulation of differentiating subpopulations of dopaminergic and
GABAergic neurons in the developing midbrain. We believe that understanding the
basic developmental mechanisms and their variation will be of importance for design
of novel diagnostics and treatment for neurological and psychiatric disorders.
PI Juha Partanen
Postdoctoral research at Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto (Laboratory of Prof. Janet
Rossant), Canada, 1994–1998
Research Director, Laboratory Animal
Center, University of Helsinki 7–12/2008
Professor of Zoology, University of Turku
1–11/2009
Professor of Genetics, University of
Helsinki since 12/2009
www.biocenter.helsinki.fi/bi/partanen
Email: juha.m.partanen@helsinki.fi
Group members
Postdoctoral fellow: Dmitri Chilov
Graduate students: Jonna Saarimäki,
Paula Peltopuro, Natalia Sinjushina,
Laura Lahti, Kaia Kala
Technician: Eija Koivunen
Undergraduate students: Sini-Maaria
Virolainen, Mia Åstrand
Kala K, Haugas M, Lilleväli K, Guimera J, Wurst W, Salminen M, Partanen J. Gata2 is a tissuespecific post-mitotic selector gene for midbrain GABAergic neurons. Development. 2009;
136: 253–62.
Turakainen H, Saarimäki-Vire J, Sinjushina N, Partanen J, Savilahti H. Transposition-based
method for the rapid generation of gene-targeting vectors to produce Cre/Flp-modifiable
conditional knock-out mice. PLoS One. 2009; 4:e4341
Saarimäki-Vire J, Peltopuro P, Lahti L, Naserke T, Blak AA, Vogt Weisenhorn DM, Ornitz D,
Wurst W, Partanen J. FGF receptors co-operate to regulate neural progenitor properties in
the developing mid- and hindbrain. J. Neurosci. 2007; 27: 8581–8592.
Jukkola T, Lahti L, Naserke T, Wurst W, Partanen J. FGF regulated gene-expression and neuronal differentiation in the developing midbrain-hindbrain region. Dev. Biol. 2006; 297: 141–157.
Trokovic R, Jukkola T, Saarimäki J, Peltopuro P, Naserke T, Vogt Weisenhorn D, Trokovic N,
Wurst W, Partanen J. Fgfr1 dependent boundary cells between developing mid- and hindbrain. Dev Biol. 2005; 278: 428–439.
Research at the Institute | Developmental Biology
The inner ear – from development
to therapeutic applications
 Identification
of key transcriptional and cell cycle regulators
in development of the inner ear sensory epithelial cells
 Regenerative biology of inner ear cells
T he inner ear sensory cells, the hair cells, are key players in hearing and
balance functions. Hair cells are postmitotic, differentiated cells. Their death due
to environmental and genetic factors is irreversible; lost cells are not replaced by
new ones. Auditory hair cell death accounts for most hearing loss, affecting substantial proportions of the population. The significance of hearing loss as a global health
problem will increase in the future. State-of-art treatment of hearing loss consists of
devices such as hearing aids and cochlear implants. They are not perfect. The advent
of regenerative medicine has kick-started the search for biological treatment strategies to restore inner ear function.
We have 2 main avenues in our research. One is to understand transcriptional
regulation of development of the inner ear sensory epithelial cells. This knowledge
is important for the design of regeneration therapies to re-grow new sensory cells,
through triggering conversion of non-sensory cells to hair cells. This transdifferentiation does not normally occur in mammalian ears, in contrast to non-mammalian
species. We have recently shown the role of the homeodomain transcription factor
Prox1 in the developing sensory epithelia (Kirjavainen et al., 2008). The antagonistic action of Prox1 on the hair cell phenotype is likely to have an inhibitory effect
on the transdifferentiation process and, thus, suppression of Prox1 activity may be
needed for full phenotypic conversion. We have continued to study the Prox1 genetic pathway and to find out the molecular mechanisms how the zinc finger factor
Gfi1, a Prox1 target gene, promotes hair cell survival.
A second avenue of our research is to understand cell cycle regulation in the inner ear. We have focused on the regulation of the maintenance of postmitotic state
of hair cells. We have identified critical negative cell cycle regulators, the retinoblastoma protein and members of the family of cyclin-dependent kinase inhibitors,
in hair cells and shown that the postmitotic state is critical for the lifelong survival
of these cells (Mantela et al., 2005; Laine et al., 2007). More recently, using mutant
mouse models and in vitro experiments we have identified cyclin D1 as a cell cycle
regulator in the sensory epithelia. We have shown that its suppression is critical for
the non-proliferative status of hair cells. In addition, we have shown that cyclin D1
expression in non-sensory cells underlies their proliferative potential (Laine et al.,
2009). These results are likely to be important for the field of inner ear sensory cell
regeneration, because stimulation of cell cycle re-entry is a central part of this process. Based on our results, cyclin D1 might be a suitable target for proliferative regeneration in the inner ear and, therefore, we currently aim to identify its upstream
regulators in this organ.
We have studied hair cell responses to forced proliferation, DNA damage and
activation of the p53 tumor suppressor. These studies have been conducted in organotypic cultures using viral-mediated gene transfer and small molecule modulators.
We have revealed the hypersensitivity of auditory hair cells to p53 induction. The
data emphasize the need of keeping p53 in check in these cells (Sulg et al., in press).
The results have important clinical implications, since ototoxicity is one of the most
severe side-effects of chemotherapeutic drugs. The data underscore the importance
of understanding the mechanisms of p53 activation in the inner ear HCs following
various types of stressors.
PI Ulla Pirvola
Postdoctoral research at the Institute of
Biotechnology, 2002–2004
Academy of Finland Research Fellow
2004–2009
www.biocenter.helsinki.fi/bi/inner_ear
Email: ulla.pirvola@helsinki.fi
Group members
Graduate students: Anna Kirjavainen,
Heidi Laine, Johanna Mantela, Marilin
Sulg.
Visiting student: Bernhard Saeger
Technician: Sari Tynkkynen
Sulg M, Kirjavainen A, Pajusola K, Bueler
H, Ylikoski J, Laiho M, Pirvola U. Differential sensitivity of the inner ear sensory cell
populations to forced cell cycle re-entry and
p53 induction. J Neurochem, in press.
Laine H, Sulg M, Kirjavainen A, Pirvola U.
Cell cycle regulation in the inner ear sensory epithelia: Role of cyclin D1 and cyclindependent kinase inhibitors. Dev Biol. 2009;
337: 134−146.
Kirjavainen A, Sulg M, Heyd F, Alitalo K, YläHerttuala S, Möröy T, Petrova TV, Pirvola U.
Prox1 interacts with Atoh1 and Gfi1, and
regulates cellular differentiation in the inner
ear sensory epithelia. Dev Biol. 2008; 321:
295−308.
Laine H, Doetzlhofer A, Mantela J, Ylikoski
J, Laiho M, Roussel MF, Segil N, Pirvola U.
p19Ink4d and p21Cip1 collaborate to maintain the postmitotic state of auditory hair
cells, their codeletion leading to DNA damage and p53-mediated apoptosis. J Neurosci.
2007; 27: 1434−1444.
Mantela J, Jiang Z, Ylikoski J, Fritzsch B,
Zacksenhaus E, Pirvola U. The retinoblastoma gene pathway regulates the postmitotic
state of hair cells of the mouse inner ear.
Development. 2005; 132: 2377−2388.
Patterning and diversification regulated by
BMP signaling in Drosophila and beyond
 Directional
transport of BMP ligands in Drosophila embryogenesis
and wing venations
B one morphogenetic proteins (BMPs) of the TGF-ß superfamily play prominent roles in metazoan developmental processes as diverse as cell proliferation,
apoptosis, differentiation, and cell-fate determination. In Drosophila, the dpp gene
is a functional ortholog of vertebrate BMP2/4 and is involved in the processes such
as dorsal patterning of the early embryo, patterning and growth of imaginal discs,
and wing vein formation. The fundamental signaling mechanism employed by BMPs
during development is conserved both in vertebrates and invertebrates. This functional conservation suggests that studies of TGF-ß signaling in Drosophila will have
an impact on our understanding of TGF-ß signaling in mammals. Furthermore, given
the role of TGF-ß type signaling in morphogenesis in Drosophila development; it is
not surprising those alterations in this pathway in humans result in aberrations in
development and tissue remodeling.
The Dpp signal is regulated by post-transcriptional level such as cleavage of precursor by furin-type proprotein convertases. We have found that cleavage sites of
the BMP2/4/Dpp family have been evolutionarily diversified. We have also found
that the Dpp precursor is cleaved at three furin sites, and the first cleavage at an
upstream furin site is critical and sufficient for long-range Dpp signaling, suggesting
that the furin cleavage sites in BMP2/4/Dpp precursors have adjusted to different
systems in diversified species.
Our previous findings indicate that the facilitated diffusion of BMP heterodimer regulates several morphogenetic events that occur at different developmental
stages. To understand how facilitated diffusion of BMP ligands produces morphogenetic diversity, we use fluorescently labeled ligands and follow their distributions in
Drosophila pupal wings. Time lapse imaging in wild type and various mutant backgrounds is used to monitor how ligands are transported from their source to their
target cells by facilitated diffusion.
PI Osamu Shimmi
PhD 1994, University of Tsukuba, Japan
Minnesota, USA, 1997–2005
Academy of Finland Research Fellow,
2005−2010
www.biocenter.helsinki.fi/bi/shimmi
Email: osamu.shimmi@helsinki.fi
Group members
Graduate students: Shinya Matsuda,
Zhao Zeng, Jaana Künnapuu, Ida Björkgren
Technician: Risa Shimmi
Undergraduate students: Evely Vridolin,
Maria Kowalski
Umulis DM, Shimmi O, O’Connor MB, Othmer HG. Organism-scale modeling of early Drosophila patterning via Bone Morphogenetic Proteins. Dev. Cell. 2010; 18(2): 260–274.
Künnapuu J, Björkgren I, Shimmi O. The Drosophila DPP signal is produced by cleavage of its
proprotein at evolutionary diversified furin-recognition sites. PNAS. 2009; 106, 8501−8506.
Akiyama T, Firkus C, Takeo S, Shimmi O, Nakato H. Molecular mechanisms of glypican co-receptor function: the role of Drosophila Dally in Dpp signaling. Dev. Biol. 2008; 313: 408−419.
Shimmi O, Ralston A, Blair SS, O’Connor MB. The crossveinless gene encodes a new member of the twisted gastrulation family of BMP binding proteins which, with Short gastrulation, promotes BMP signaling in the crossveins of the Drosophila wing. Dev. Biol. 2005; 282:
70−83.
Shimmi O, Umulis D, Othmer H, O’Connor MB. Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell.
2005; 120: 873−886.
Research at the Institute | Developmental Biology
Regulation of ectodermal organ development
 Intercellular
communication regulating formation of ectodermal
organs (teeth, hairs, and glands)
 Mouse models and organ cultures to analyse functions of FGF,
TGFb, Hedgehog, Wnt and Ectodysplasin (Eda) pathways
W e explore the mechanisms that regulate the formation of ectodermal
organs, including teeth, hairs and glands. We focus on signalling networks
mediating intercellular communication, and examine how they regulate the patterns, numbers, sizes, and shapes of organs. The results may have clinical implications in the diagnosis, prevention and treatment of congenital defects as well as in
the design of regenerative therapies.
We use mouse models and organ culture techniques to analyse the functions of
conserved signal pathways including FGF, TGFß, Hedgehog, Wnt and Ectodysplasin
(Eda). Some of the mice are models for human syndromes such as ectodermal dysplasias and tooth agenesis. Our major interest is the formation of placodes initiating
the development of all ectodermal appendages. We have shown previously that the
Eda pathway stimulates ectodermal placode formation, and we recently identified
a number of Eda receptor (Edar) targets by microarray analysis. Interestingly, these
include both positive and negative effectors of other conserved signal pathways
including Shh and Dkk4, respectively. We have demonstrated that Edar is the main
activator of NF-κB signalling in developing skin appendages. However, we discovered that there is functional overlap of Edar signal pathway with Troy, another TNF
receptor in hair follicle formation, and that this is likely to be mediated by NF-κB
independent pathways. Several mouse models are currently used to examine the
modulation of Wnt signaling and the integration of Wnt with Eda and the other
conserved pathways. We have shown that Wnt signal activation in the ectoderm
induces continuous tooth formation, extra whiskers and hairs, and accelerates hair
initiation and impairs patterning. We have continued studies on epithelial stem cell
maintenance, proliferation and differentiation in a stem cell niche which we discovered in teeth. Our results indicate that the mesenchyme adjacent to the epithelial
stem cell niche regulates stem cell functions by several key signals, and that there is
a complex integrated network of signals including FGFs, Activin and BMPs. We also
examine the mechanisms of tooth replacement by using the ferret as model animal.
Närhi K, Järvinen E, Birchmeier W, Taketo M, Mikkola MM, Thesleff I. Sustained epithelial ßcatenin activity induces precocious hair development but disrupts hair follicle down-growth
and hair shaft formation. Development. 2008; 135: 1019−1028.
Pummila M, Fliniaux I, Jaatinen R, James M, Laurikkala J, Schneider P, Thesleff I, Mikkola ML.
Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of BMP activity and
induction of Shh expression. Development. 2007; 134: 117−125.
Wang X-P, Suomalainen M, Felszeghy S, Zelarayan LC, Alonso MT, Plikus MV, Maas R, Chuong,
CM, Schimmang T, Thesleff I. An integrated gene regulatory network controls epithelial stem
cell proliferation in teeth. PLoS Biol. 2007; 5: 1324−1333.
Järvinen E, Salazaar-Ciudad I, Birchmeier W, Taketo MM, Jernvall J, Thesleff I. Continuous
tooth generation in mouse is induced by activated epithelial Wnt/ ßcatenin signalling. PNAS.
2006; 103: 18627−18632.
Laurikkala J, Mikkola ML, James M, Tummers M, Mills A, Thesleff I. P63 regulates multiple
signalling pathways required for ectodermal organogenesis and differentiation Development.
2006; 133: 1553−1563.
PI Irma Thesleff
Research Director at the Institute
since 1996
Postdoctoral research at NIDCR, NIH,
Bethesda, MD, USA, 1978–1979
Professor and Chairman, Department of
Pedodontics and Orthodontics, University of Helsinki, 1990−2004
Academy Professor, Academy of Finland,
1998–2003
EMBO member, 2000
AAAS Fellow, 2008
www.biocenter.helsinki.fi/bi/thesleff
Email: irma.thesleff@helsinki.fi
Group members
Senior scientist: Marja Mikkola
Postdoctoral fellows: Frederic Michon,
Mark Tummers, Toshiyuki Yoshida,
Päivi Lindfors, Kan Saito
Graduate students: Otso Häärä, Maria
Jussila, Sylvie Lefebvre, Katja Närhi,
Vera Shirokova, Marika Suomalainen,
Maria Voutilainen
Technicians: Merja Mäkinen, Riikka
Santalahti, Raija Savolainen (jointly with
Jukka Jernvall)
Undergraduate student: Elisa Rysti
Genome Biology
Regulation of gene expression
in eukaryotic systems
 Post-transcriptional
regulation of gene expression
by the U12-dependent spliceosome
 Genomics of ecological model systems
O ur research has two main focus areas, both related to eukaryotic gene
expression. First, we are studying the mechanism and regulation of eukaryotic
gene expression by the U12-dependent spliceosome. We use RNA biochemistry and
various model organisms (human cell lines, Drosophila and mouse) to investigate the
mechanism and regulation of RNA splicing both in vitro and in vivo. Second, we are
developing and using genomic tools for the Glanville fritillary (Melitae cinxia) butterfly to study the effect of gene expression on butterfly population structure in the
Åland Islands.
The key aim of our research is to understand the role of U12-dependent spliceosome, and more generally, the significance of having two separate spliceosomes in
the cells of higher eukaryotes. We (Pessa et al. 2006) and others have found that
the U12-type introns are spliced more slowly than the normal U2-type introns, but
splicing takes place in the nucleus similarly to normal U2-type introns (Pessa et al.,
2008). This suggests that the primary role of U12-dependent introns could be a regulatory module that provides rate-limiting post-transcriptional control to a defined
group of genes at the level of pre-mRNA splicing. Our recent detailed biochemical
investigations on the intron recognition have uncovered novel RNA-RNA and RNAprotein interactions near the 5’ splice site (Frilander & Meng, 2005; Turunen et al.,
2008), and revealed an evolutionarily highly conserved regulatory mechanism that
will be the key focus of our future work.
On our ecological genomic project we have recently successfully used massive
parallel sequencing methods for the analysis of transcriptomes (Vera et al., 2008)
which has led to the development of microarrays and related genomic tools for
organism that are not laboratory model organisms. Our future research on these
organisms will heavily use deep sequencing methods in the analysis of genomes,
transcriptomes, and post-transcriptional regulation.
PI Mikko Frilander
Postdoctoral research at Yale School of
Medicine, New Haven, USA, 1997–2000
Project Leader at the Institute 2000–
2001
www.biocenter.helsinki.fi/bi/splicing
Email: mikko.frilander@helsinki.fi
Group members
Graduate students: Elina Niemelä, Heli
Pessa, Janne Turunen, Jens Verbeeren,
Jouni Kvist (jointly with Professor Ilkka
Hanski)
Technician: Marja-Leena Peltonen
Undergraduate students: Trang Nguyen
Hong, Visa Nurmi
Metapopulation Research
http://www.helsinki.fi/science/
metapop/index.htm
Sundström JF, Vaculova A, Smertenko AP, Savenkov EI, Golovko A, Minina E, Tiwari BS, Rodriguez-Nieto S, Zamyatnin AA Jr, Välineva T, Saarikettu J, Frilander MJ, Suarez MF, Zavialov A,
Ståhl U, Hussey PJ, Silvennoinen O, Sundberg E, Zhivotovsky B, Bozhkov PV. Tudor staphylococcal nuclease is an evolutionarily conserved component of the programmed cell death
degradome. Nat Cell Biol. 2009; 11: 1347– 1354.
Pessa HKJ, Will CL, Meng X, Schneider C, Watkins NJ, Perälä N, Nymark M, Turunen JJ, Lührmann R, Frilander MJ. Minor spliceosome components are predominantly localized in the
nucleus. PNAS. 2008; 105, 8655– 8660.
Turunen JJ, Will CL, Grote M, Lührmann R, Frilander MJ. The U11-48K Protein Contacts the
5‘ Splice Site of U12-Type Introns and the U11-59K Protein. Mol Cell Biol. 2008; 28: 3548–
3560.
Vera JC, Wheat CW, Fescemyer HW, Frilander MJ, Crawford DL, Hanski I, Marden JH. Rapid
transcriptome characterization for a nonmodel organism using 454 pyrosequencing. Mol
Ecol. 2008; 17: 1636– 1647.
Pessa H, Ruokolainen A, Frilander MJ. The abundance of the spliceosomal snRNPs is not limiting the splicing of U12-type introns. RNA. 2006; 12, 1883– 1892.
Research at the Institute | Genome Biology
Genetic control of wood development
 Cytokinins
and other genetic regulators of stem cell identity in
wood and Arabidopsis
 Regulating cell fate through manipulation of the bifunctional
kinase-phosphatase cytokinin receptor
W ood is derived from stem cells that occur as a cylindrical sheet in the
trunk of a tree. We investigate how genes regulate these stem cells. We are
investigating this process in tree systems and in the more amenable Arabidopsis.
We have shown that cytokinin phytohormones are important regulators underlying
cambial development.
In Arabidopsis we have identified two genes (the first CRE1/WOL encodes a cytokinin receptor, the second AHP6 encodes a regulator of cytokinin signalling) which
have allowed us to show that cytokinins promote stem cell identity during root
development in Arabidopsis. Decrease in cytokinin activity causes all vascular cells to
differentiate into protoxylem cells. AHP6, an inhibitory protein, counteracts cytokinin signaling in a spatially specific manner thereby allowing protoxylem formation.
We have also shown that CRE1/WOL cytokinin receptor is a bifunctional kinase/
phosphatase, and elimination of the negatively regulating phosphatase activity of
the CRE1/WOL results in stimulation of proliferation of vascular cell files. This indicates that in addition to specifying vascular cell identity, cytokinins have a second
role in controlling the rate of proliferation of vascular cell files.
An obvious next question is how much the Arabidopsis genetic information applies to economically important plants. We have reduced cytokinin levels endogenously by engineering transgenic poplar trees (P. tremula x tremuloides) to express
a cytokinin catabolic gene, Arabidopsis CYTOKININ OXIDASE 2. Transgenic trees
showed reduced concentration of a biologically active cytokinin, correlating with
impaired cytokinin responsiveness. In these trees, the radial growth and cambial
activity was specifically compromised. Together, our results show that cytokinins are
major hormonal regulators required for cambial development.
Selected publications:
Nieminen K, Immanen J, Laxell M, Kauppinen L, Tarkowski P, Dolezal K, Tähtiharju S, Elo A,
Decourteix M, Ljung K, Bhalerao R, Keinonen K, Albert VA, Helariutta Y. Cytokinin signaling
regulates cambial development in poplar. PNAS. 2008; 105(50): 20032–7.
Mähönen AP, Bishopp A, Higuchi M, Nieminen KM, Kinoshita K, Törmäkangas K, Ikeda Y, Oka
A, Kakimoto T, Helariutta Y. Cytokinin signaling and its inhibitor AHP6 regulate cell fate during vascular development. Science. 2006; 311: 94–98.
Mähönen AP, Higuchi M, Törmäkangas K, Kinosita K, Pischke M, Sussman MR, Helariutta Y,
Kakimoto T. Cytokinins regulated bidirectional phosphorelay network. Curr Biol. 2006; 16:
1116–1122.
Tuskan GA et al. The genome of black cottonwood, Populus trichocarpa (Torr. & Gray). Science. 2006; 313: 1596–604.
PI Yrjö Helariutta
Postdoctoral research at New York
University/ New York Botanical Garden,
1995–1998
Research Director/Professor, Institute
of Biotechnology/Dept. of Bio. and Env.
Sciences, University of Helsinki, Finland
since 2006
EMBO Young Investigator Programme
(EMBO YIP) Award, 2001
European Young Investigator (EURYI)
Award, 2005
EMBO member, 2008
www.biocenter.helsinki.fi/bi/Helariutta
Email: yrjo.helariutta@helsinki.fi
Group members
Postdoctoral fellows: Anthony Bishopp,
Ana Campilho, Jan Dettmer, Satu Lehesranta, Annakaisa Elo, Kamil Ruzicka, Jing
Zhang
Graduate students: Kaisa Nieminen,
Anne Honkanen, Juha Immanen, Sedeer
El-Showk, Hanna Help, Raffael Lichtenberger, Robertas Ursache
Technicians: Katja Kainulainen,
Mikko Herpola
Group is member of Academy
Plant Signal Research
http://www.helsinki.fi/bioscience/plantsignal/english/index.
htm
Bioinformatics group
 Elucidating
functional correlates from sequence and structure
T he complete genomic sequence of over a hundred organisms, including several higher eukaryotes, has been determined. We develop and use a wide range
of computational tools to make sense of this book of life. The overall goal is to
model evolutionary relationships in sequence and structure data and to elucidate
their functional correlates.
Proteins can be clustered based on sequence (or structure) similarities and classified into families which derive from a common ancestor. The members of a family
may inherit complex properties from the ancestor. We have for a long time produced
evolutionary classifications of all known proteins based on sequence and structure
comparisons. The analysis of variation and conservation reveals functional signature
motifs which can ultimately lead to an accurate mapping of protein functions.
Our group has gotten involved in the annotation of the genomes of pro-biotic
and pathogenic bacteria sequenced on campus, and our tools have been used to
analyze functional genomics data generated by collaborating research groups. For
example, we have developed tools to locate pilus operons and for rapid function annotation of large protein sets.
A particular focus is on the statistical analysis of differential gene expression data
with the aim to detect which functional classes are perturbed in the experiment.
We propose a novel test statistic which outperforms existing methods when detecting biological signal. Bayesian statistics and segmentation algorithms applied to
genomic datasets have revealed several interesting signal areas.
PI Liisa Holm
Postdoctoral researcher and group leader
at EMBL, 1990–2002
EMBO member, 2009
http://www.bioinfo.biocenter.helsinki.fi/
Email: liisa.holm@helsinki.fi
Group members
Senior scientist: Petri Törönen
Graduate students: Samuli Eldfors,
Matti Kankainen, Patrik Koskinen,
Ilja Pljusnin, Xuan Hung Ta
Technician: Päivi Rosenström
Undergraduate students: Teija Ojala,
Hitomi Hasegawa, Emmanuel Ojefua
Finn R, Mistry J, Tate J, Coggill P, Heger A, Pollington J, Gavin OL, Ceric G, Forslund K, Holm
L, Sonnhammer ELL, Eddy S, Bateman A. The Pfam protein families database. Nucl. Acids
Res. Database issue. 2010. In press.
Hasegawa H, Holm L. Advances and pitfalls of protein structural alignment. Curr. Opin.
Struct. Biol. 2009; 19: 381−389.
Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, Satokari R,
Vesterlund S, Hendrickx APA, Lebeer S, De Keersmaecker SCJ, Vanderleyden J, Hämäläinen
T, Laukkanen SI, Salovuori N, Ritari J, Alatalo E, Korpela R, Mattila-Sandholm T, Lassig A,
Hatakka K, Kinnunen KT, Karjalainen H, Saxelin M, Laakso K, Surakka A, Palva A, Salusjärvi T,
Auvinen P, de Vos WM. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals
pill containing a human-mucus binding protein. PNAS. 2009; 106: 17193−17198.
Plyusnin I, Holm L, Kankainen M. LOCP − locating pilus operons in Gram-positive bacteria.
Bionformatics. 2009; 25: 1187−1188.
Törönen P, Ojala P, Marttinen P, Holm L. Robust extraction of functional signals from gene
set analysis using a generalized threshold free scoring function. BMC Bioinformatics. 2009;
10: 307.
Research at the Institute | Genome Biology
Kinase signaling linking metabolism
and growth control
 Signaling by the metabolic regulator and tumor supressor kinase
 Transcriptional regulation by cyclin-dependent kinases Cdk7 and
LKB1
Cdk8 in growth and differentiation
M ajor human diseases such as diabetes and cancer are due to deregulated signaling stemming from genetic alterations and extrinsic factors. Signaling
in pathways and in larger networks typically involves sequential activation of kinases
phosphorylating substrates and thus relaying and amplifying signals ultimately modulating transcriptional responses in target gene sets. Our longstanding interest is to
characterize signaling pathways regulating mammalian cell growth and how these
impinge on transcriptional responses in human disease.
Two critical mediators of transcriptional responses involved in cancer and metabolism are the transcriptional kinases Cdk7 and Cdk8 mediating signals to RNA
polymerase II. We are investigating the molecular mechanisms and in vivo functions
of Cdk7 and Cdlk8 combining mouse molecular genetics with Drosophila knockdown
strategies and cell-based screening approaches. Recent discoveries include identifying that Cdk7 acts as a roadblock to adipogenesis and that this presumed ubiquitous
basal transcription factor is not expressed in fat tissues. Our goal is to understand
the basis for the specificity of transcriptional regulation by metazoan Cdk7 and
Cdk8 and their contribution to growth control and differentiation.
One of the rare kinases acting normally to restrict tumor growth is the LKB1serine/threonine kinase critical for activation of at least 14 related kinases involved
in metabolism and polarity regulation. We are interested in how LKB1 mediates its
tumor suppressing function, and recently identified that LKB1 signaling in mesenchymal cells is required for suppression of epithelial hyperproliferation in a mouse
polyposis model and likely also in the human Peutz-Jeghers syndrome. We are currently extending investigations of tumor suppression mechanisms of the LKB1 tumor suppressor kinase from hereditary polyposis to sporadic cancer (lung, uterine
cervix). For this a combination of tissue- and cell type specific targeting approaches
in vivo (conditional mouse models) and in vitro (2D and 3D RNAi & conditional deletions) of LKB1 and LKB1 substrate mutations will be used with a specific interest in
the Nuak2 and AMPK kinases and cytoskeletal regulation.
Helenius K, Yang Y, Alasaari J, Mäkelä TP. Mat1 is required for PPARg-mediated adipocyte differentiation. Mol. Cell. Biol. 2009; 29(2):315−23.
Wu J, Vallenius T, Ovaska K, Westermarck J, Mäkelä TP, Hautaniemi S. Integrated network
analysis platform for protein-protein interactions. Nat Methods. 2009;6(1):75–7.
Katajisto P, Vaahtomeri K, Ekman N, Ventelä E, Ristimäki A, Bardeesy N, Feil R, DePinho RA,
Mäkelä TP. LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal
polyposis. Nat Genet. 2008; 40(4): 455−9.
Londesborough A, Vaahtomeri K, Tiainen M, Katajisto P, Ekman N, Vallenius T, Mäkelä TP.
LKB1 in endothelial cells is required for angiogenesis and TGFbeta-mediated vascular smooth
muscle cell recruitment. Development. 2008; 135(13): 2331−8.
Vaahtomeri K, Ventelä E, Laajanen K, Katajisto P, Wipff PJ, Hinz B, Vallenius T, Tiainen M,
Mäkelä TP. Lkb1 is required for TGFbeta-mediated myofibroblast differentiation. J Cell Sci.
2008; 121(Pt 21):3531–40.
PI Tomi P. Mäkelä
Director of BI since 1.7.2009
MD; PhD 1992, University of Helsinki,
Finland
Postdoctoral research at Whitehead
Institute for Biomedical Research, MIT,
1993−1995
Professor of Biochemistry and Molecular
Biology, University of Helsinki,
since 2003
Co-director, Centre of Excellence in
Translational Genome-Scale Biology,
2006−2011
EMBO member, 2003
Member of the Finnish Academy
of Science and Letters, 2002
http://www.biocenter.helsinki.fi/bi/
makela
Email: tomi.makela@helsinki.fi
Group members
Postdoctoral fellows: Tea Vallenius,
Pekka Katajisto, Jianmin Wu, Rafael
Martinez, Saara Ollila
Graduate students: Lina Udd,
Kari Vaahtomeri, Katja Helenius,
Timofey Tselykh, Emilia Kuuluvainen,
Yang Ying, Kaisa Laajanen, Yajing Gao,
Anou Londesborough
Technicians: Saana Laine, Outi Kokkonen
(partly core facility)
Undergraduate students: Bianca Kovac
(née Negruti), Michelle Sahal-Estime
Genome-Biology Unit Core Facility:
Tea Vallenius, Rafael Marinez, Kirsi Mänttäri, Outi Kokkonen (partly core facility)
Group is a member of Academy
of Finland Centre of Excellence
in Translational Genome-Scale
Biology
http://tgsb.vtt.fi/
MTT/BI Plant Genomics Laboratory
 Retrotransposons as drivers of genomic dynamics
 Identification of disease resistance and quality trait
genes
through functional genomics
T he MTT/BI Plant Genomics Laboratory is a joint laboratory of the Institute
of Biotechnology and of MTT Agrifood Research Finland. At MTT, the lab belongs to the Genomics Research programme, which includes plants, animals, and
microbes, directed by Prof. Alan H. Schulman within the Department of Biotechnology and Food Research. Plant Genomics has two laboratories, the MTT/BI joint lab
at Viikki and a laboratory at Jokioinen, which work together and comprise about 30
members. The MTT/BI group studies retrotransposons as drivers of genomic change
and as markers for this change, uses these and other marker systems for map-based
cloning of genes for disease resistance and quality traits, and analyses the role
of candidate genes through the application of functional genomics tools such as
microarrays. To support these goals, the Jokioinen lab develops and applies doubledhaploid populations for mapping in barley, rye, oat, and Brassica and maps traits in
these crops. We also have implemented barley transformation using Agrobacterium.
Potato di-haploids and fusions have been produced and are being used to develop
novel glycoalkaloids as pharmaceutical lead compounds.
The Plant Genomics group has a long-term programme to understand the role
of retrotransposons in genome dynamics. These mobile elements replicate in a way
similar to retroviruses and create daughter copies that integrate throughout the
genome. We are working to establish the details of their lifecycle, the role of cellular regulation of their capacity for enormous copy number increase and mutagenic
genome disruption, and their effect on genomic and cellular function. Members of
the group are currently studying transcriptional regulation of the barley BARE retrotransposons of barley and the translation, processing and the assembly of viruslike particles. We are also investigating how successful non-autonomous retrotransposons, especially Cassandra, parasitize other retrotransposons for needed proteins
and evade cellular regulation by using novel pol III transcription.
PI Alan Schulman
PhD 1986, Yale University, New Haven,
Connecticut USA
Helsinki, 1986–1988
Professor of Plant Biotechnology, MTT,
Finland, since 2001
Head, Genomics Research, MTT, since
2006
www.biocenter.helsinki.fi/bi/bare-1_
html
Email: alan.schulman@helsinki.fi
Group members
Senior scientist: Ruslan Kalendar
Postdoctoral fellow: Cedric Moisy
Graduate students: Chang Wei,
Marko Jääskeläinen, Jaakko Tanskanen
Technicians: Ursula Lönnqvist, Anne-Mari
Narvanto
Vogel JP, Garvin DF, Rokshar D, Bevan MW et al. Genome sequence analysis of the model
grass Brachypodium distachyon. Nature 2010; 463:763–768.
Schulte D, Close TJ, Graner A, Langridge P, Matsumoto T, Muehlbauer G, Sato K, Schulman
AH, Waugh R, Wise RP, Stein N. The International Barley Sequencing Consortium (IBSC) – at
the threshold of efficient access to the barley genome. Plant Physiology. 2009; 49: 142–147.
Chang W, Schulman AH. The BARE retrotransposon produces multiple groups of rarely polyadenylated transcripts from two differentially regulated promoters. Plant Journal. 2008; 56:
40–50.
Kalendar R, Tanskanen J, Chang W, Antonius K, Sela H, Peleg O, Schulman AH. Cassandra retrotransposons carry independently transcribed 5S RNA. PNAS. 2008; 105: 5833–5838.
Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell AJ, Leroy P, Morgante
M, Panaud O, Paux E, SanMiguel P, Schulman AH. A unified classification system for eukaryotic transposable elements. Nature Rev. Genet. 2007; 8: 973–982.
Structural Biology & Biophysics
Physical foundations of evolutionary theory
 Clarification
of thermodynamic imperatives in network
organization and exemplification in the context of neural and other
communication networks
 Clarification of physical foundations of mathematical biology
T he theory of evolution by natural selection is often regarded as the most
general description of living nature. Nevertheless our understanding of nature as
a whole has remained impaired because Darwin’s tenet, despite its broad scope and
central role, is a phenomenological description without a physical basis given in a
mathematical form.
It is no new thought to suspect that evolution is a manifestation of the 2nd
law of thermodynamics. However, this conjecture was proven first when the equation of evolution was derived from first principles. The ubiquitous natural law states
simply that energy differences will decrease in least time. Species are mechanisms
of transduction that acquire energy from their respective surroundings, ultimately
from insolation. The flows of energy will naturally select those mechanisms that will
level off energy differences most rapidly.
The physical portrayal of evolution has allowed us to understand several profound
questions and puzzles, most notably: why evolution is a non-deterministic process,
why nature organizes itself in a hierarchy of systems within systems, why protein
folding is difficult to predict, why population distributions are skewed and their
cumulative curves, such as species-area relationship, are power-laws. Moreover, the
statistical theory of open systems has given us understanding what is the meaning
of information and where do the laws of economy, such as the law of supply and
demand, come from.
The holistic and scale-independent view of nature provided by the 2nd law of
thermodynamics points out that natural selection does not operate only on genes
but on all matter. During evolution flows of energy naturally select the steepest
descents, equivalent to the paths of least action, and flatten non-Euclidean energy
landscape in least time. The thermodynamic theory roots biology via chemistry to
physics and widens contemporary discourse on the fundamentals of evolution.
Annila A, Kuismanen E. Natural hierarchy emerges from energy dispersal. Biosystems 2009:
95; 227–233.
Annila A, Salthe S. Economies evolve by energy dispersal. Entropy 2009; 11: 606–633.
Karnani M, Pääkkönen K, Annila A. The physical character of information. Proc. R. Soc. A.
2009; 465: 2155–2175.
Sharma V, Kaila VRI, Annila A. Protein folding as an evolutionary process. Physica 2009; 388;
851–862.
Tuisku P, Pernu TK, Annila A. In the light of time. Proc. R. Soc. A. 2009; 465: 1173–1198.
PI Arto Annila
PhD 1991, Helsinki University of
Technology, Finland
Postdoctoral research at Lund University,
Sweden, 1991
Professorship in Biophysics since
2001 together with Institute of
Biotechnology, Department of Physics
and Department of Biological and
Environmental Sciences
www.helsinki.fi/~aannila/arto
Email: arto.annila@helsinki.fi
Understanding virus evolution
through structure
 Hypothesis
on virus evolution and origins: there are only a
limited number of ways that a virion can be constructed
 Characterization of prokaryotic viruses from ecological niches
e.g. human bacterial infections to test hypothesis
I t has been estimated that there are 1031–1032 viruses in the biosphere. This
number exceeds the number of their host cells by at least one order of magnitude. Consequently practically every organism is constantly under viral attack and
viruses may cause the highest selection pressure that cellular organisms encounter.
Viruses play an important role as obligate cellular parasites ensuring their own reproduction and modulating their host cells. Due to their adverse effects on the well
being of their host organism, the emphasis in virology has focused on detection and
prevention of pathogenic viruses infecting humans and domesticated animals and
plants. However, how the entire domain of viruses is organized, what is the origin
of viruses and how they evolve are deep questions in biology in general and in virology in particular.
Our research has advanced by discovering how viral molecular machines work,
what determines the size in certain icosahedral viruses, how a complex infectious
viral particle self-assembles from its purified structural constituents, and how the
RNA dependent RNA polymerases operate. The accumulating information on virus
structures has led to a surprising new hypothesis on virus evolution and origins.
It is postulated that there are only a limited number of ways that a virion can be
constructed.
The underpinning hypothesis is that we can probe deep evolutionary relationships
in general and for viruses in particular by combining structural and functional information. We wish to test the hypothesis that prokaryotic viruses are homologues to
viruses infecting multicellular eukaryotic organisms. Recognizing such connections
will also lead to major revisions in how we classify viruses.
Currently we have combined virology, genetics, biochemistry, biophysics and
structural analysis to describe in detail the viral model systems under study (predominantly viruses infecting prokaryotic hosts). We are now extending to virus
ecology by isolating and characterizing prokaryotic viruses from different ecological niches such as human bacterial infections, highly saline and high temperature
environments to test our hypothesis and to allow us to search for novel virus types
with unknown structural principles.
Abrescia NG, Grimes JM, Kivela HM, Assenberg R, Sutton GC, Butcher SJ, Bamford JK, Bamford DH, Stuart DI. Insights into virus evolution and membrane biogenesis from the structure
of the marine lipid-containing bacteriophage PM2. Mol. Cell. 2008; 31(5): 749−761.
Krupovic M, Bamford DH. Virus evolution: How far does the double beta-barrel viral lineage
extends? Nat Rev Microbiol. 2008; 6 (12): 941−948.
Bamford DH, Grimes JM, Stuart DI. What does structure tell us about virus evolution? Curr
Opin Struct Biol. 2005; 15(6): 655−663.
PI Dennis Bamford
Postdoctoral EMBO fellow, Public Health
Research Institute of the City
of New York, 1981−1982
Professor in General Microbiology
since 1993
Director of the Centre of Excellence
in Structural Virology, 2000−2005
Academy Professor, 2002−2007
EMBO Member, 2006
Director of the Centre of Excellence
in Virus Research 2006−2011
www.helsinki.fi/virres
Email: dennis.bamford@helsinki.fi
Group members
Senior scientists: Minna Poranen, Elina
Roine, Hanna Kivelä, Janne Ravantti
Postdoctoral fellows: Gabija Ziedaite
Graduate students: Antti Aalto, Andrius
Buivydas, Virginja Cvirkaite-Krupovic,
Silja Jaatinen, Miao Jiang, Mart Krupovic,
Maija Pietilä, Peter Sarin
Technicians: Linda Degerth,
Sari Korhonen, Eija Stenius,
Riitta Tarkiainen
Undergraduate students: Jari Hirvonen,
Xiaoyu Sun, Nina Atanasova
Group is a part of Academy
of Finland Centre of Excellence
in Virus Research
Research at the Institute | Structural Biology & Biophysics
Macromolecular structure and function
 How
structure, function and interactions of proteins and lipids
influence disease
O ur research interests are primarily focused on the structure, function
and interactions of biological molecules, mainly proteins and lipids, and their
influence on disease. The majority of current drugs affect membrane proteins and
yet there is very little structure-based drug-design on these recalcitrant molecules.
We combine electron cryo-microscopy, three-dimensional image reconstruction and
X-ray crystallography to image these molecules within large complexes such as viruses and their interaction with cell-surface proteins used for host recognition. Recently we have made significant advances in determining the structures of several
membrane-containing viruses, including the X-ray determination of the bacterial
virus PM2 (Abrescia et al. 2008). We have as well determined sub-nanometer resolution structures of the first euryarchaeal virus, SH1, the thermophilic virus P23-77
and several picornaviruses (Jäälinoja et al. 2008; Jaatinen et al. 2008; Seitsonen et al.
2008). These studies have shed light on membrane biogenesis, membrane-protein
interactions, viral evolution and receptor-host interactions (Abrescia et al. 2008;
Huiskonen et al. 2007; Jäälinoja et al. 2008; Jaatinen et al. 2008). To complement
these studies, we have collaborated with Pekka Lappalainen’s group to look at proteins that modulate membrane function in cells such as the I-BAR domain proteins
(Saarikangas et al. 2009).
Polianskyte Z, Peitsaro N, Dapkunas A, Liobikas J, Soliymani R, Lalowski M, Speer O, Seit
sonen J, Butcher S, Cereghetti GM, Linder MD, Merckel M, Thompson J, Eriksson O. LACTB is
a filament-forming protein localized in mitochondria. PNAS. 2009; 106: 18960–18965.
Psencik J, Collins AM, Liljeroos L,Torkkeli M, Laurinmäki P, Ansink HM, Ikonen TP, Serimaa RE,
Blankenship RE, Tuma R, Butcher SJ. Structure of chlorosomes from the green filamentous
bacterium Chloroflexus aurantiacus. J. Bact. 2009; 191: 6701–8.
Saarikangas J, Zhao H, Pykäläinen A, Laurinmäki P, Mattila P, Kinnunen P, Butcher SJ, Lappalainen P. Molecular mechanisms of membrane deformation by I-BAR domain proteins. Curr
Biol. 2009; 19: 95–107.
Jäälinoja HT, Roine E, Laurinmäki P, Kivelä HM, Bamford DH, Butcher SJ. Structure and host
cell interaction of SH1, a lipid-containing, halophilic euryarchaeal virus. PNAS. 2008; 105:
8008–8013.
Huiskonen JT, Manole V, Butcher SJ. A tale of two spikes in bacteriophage PRD1. PNAS. 2007;
104: 6666–6671.
PI Sarah Butcher
PhD 1995, Birkbeck College, University of
London and European Molecular Biology
Laboratory, Heidelberg, Germany
Postdoctoral research European Molecular
Biology Laboratory, Heidelberg, Germany,
1996; MRC Virology Unit, Glasgow UK,
1996–1998; Institute of Biotechnology,
Professor of Structural Biology,
University of Helsinki since 2008
www.biocenter.helsinki.fi/bi/butcher
Email: sarah.butcher@helsinki.fi
Group members
Postdoctoral fellows: Katarina Hattula,
Juha Huiskonen, Harri Jäälinoja, Ari Ora
Graduate students: Lassi Liljeroos,
Violeta Manole, Jani Seitsonen,
Lotta Happonen
Technicians: Pasi Laurinmäki,
Benita Löflund, Antti Salminen
Undergraduate student:
Annunciato Pennino
Group is a part of Academy
Virus Research
Macromolecular Structures Group
 How membrane-integral and membrane-associated proteins
 Complexes of GDNF with its specific co-receptor, GFRa1
work
O ur goal is to understand the structure and function of various biological systems at the atomic level, in particular membrane-integral and membraneassociated proteins. We wish to understand how they work – whether in transmitting signals, in binding to other proteins, or in pumping protons to conserve energy.
We primarily use x-ray crystallography, supplemented with functional, mutagenesis
and theoretical studies.
We have solved the structures of two different complexes of GDNF with its specific co-receptor, GFR1, showing that the R171-E62GDNF-R224 triplet at the centre
of the complex is supported by different interactions in different GDNF-like ligands
(GFLs)-GFR pairs. Different GFL-GFR complexes differ because the bend angle between the two monomers in the GFL dimer differs. This changes the relative position of the GFRs and thus how RET positions and signals. We have also solved the
structure of another neurotrophic factor, MANF, the first one with an identified
Drosophila homologue. Its structure explains why MANF can be both cytoprotective
and neuroprotective; the N-terminal domain is a SAPLIP; it interacts with membranes, while the unstructured C-terminal domain helps fold proteins in the ER. We
are also studying integral membrane proteins, like the Yersinia adhesion protein A,
a trimeric autotransporter pathogenic protein and its homologues, and have solved
the structure of a novel E. coli immunoglobulin binding protein. This work aims at
understanding the structural basis of adhesion and the mechanism of autotransport.
Other work focuses on channels and pumps.
Our goals include complete understanding of the structural basis of the GDNFGFR signalling system because it can signal in three different ways through at
least two different molecules. The work could lead to new diagnostics and therapeutics. In addition, we intend to study the workings of the other molecules described
above, such as YadA, related proteins like the Eibs, KCC2 and pyrophosphatases. Our
work links structure and function, design and therapeutics.
Parkash V, Lindholm P, Peränen J, Kalkkinen N, Oksanen E, Saarma M, Leppänen V-M, Goldman A. The structure of the conserved neurotrophic factors MANF and CDNF explains why
they are bifunctional. Protein Eng Des Sel. 2009; 22: 233–241.
Parkash V, Leppänen V-M, Virtanen H, Jurvansuu JM, Bespalov MM, Sidorova YA, RunebergRoos P, Saarma M, Goldman A. The structure of the glial cell line-derived neurotrophic factorcoreceptor complex: insights into RET signaling and heparin binding. J. Biol. Chem. 2008;
283: 35164–35172.
Oksanen E, Ahonen A-K, Tuominen H, Tuominen V, Lahti R, Goldman A, Heikinheimo P. A
complete structural description of the catalytic cycle of yeast pyrophosphatase. Biochemistry. 2007; 46: 1228–1239.
Jokiranta TS, Jaakola V-P, Lehtinen MJ, Pärepalo M, Meri S, Goldman, A. Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome. EMBO J. 2006; 25: 1784–1794.
Nummelin H, Merckel MC, Leo JC, Lankinen H, Skurnik M, Goldman A. The structure of Yersinia adhesin YadA collagen-binding domain is a novel left-handed parallel ß-roll. EMBO J.
2004; 23: 701–711.
PI Adrian Goldman
PhD 1985, Yale University, USA
Postdoctoral research at Yale University,
1985–1987
Assistant Professor, Waksman Institute,
Rutgers University, USA, 1988–1992
Senior Scientist, Turku Centre for
Biotechnology, Finland, 1992–1998
Professor, Biotechnology and Biochemistry, University of Turku, Finland,
1998–1999
Research Director, Institute of Biotechnology since 2008
www.biocenter.helsinki.fi/bi/xray/
adrianindex.html
Email: adrian.goldman@helsinki.fi
Group members
Postdoctoral fellows: Tommi Kajander,
Jaana M. Jurvansuu, Andrzej Lyskowski,
Sanjay Sarkhel
Graduate students: Esko Oksanen, Jack
C. Leo, Juho Kellosalo, Vimal Parkash,
Anne-Sisko Patana, Harikanth Venkannagari
Visiting student: Elena Alvarez
Technicians: Maria Rehn, Katja Rosti,
Danielle Bansfield, Suzan Cingi (part of
the year)
Protein transport and glycosylation
 Protein
structures as tool to understand molecular basis of
hydrolytic lysosomal activity and its hereditary dysfunction
L ysosomal Storage Disorders (LSDs) are inherited group of diseases, caused by
mutations in individual lysosomal enzymes or in proteins involved in recognition
and transport of lysosomal proteins, and carriers of these diseases may be overpopulated in severe diseases of the elderly, such as Parkinson’s. A number of LSDs
are treated with enzyme replacement therapy (ERT) or small molecules acting as
chaperones to increase endogenously produced lysosomal activity. Improvement of
the LSD-therapies and selection of suitable therapy for individual patients requires
molecular level understanding of the lifecycle and formation of lysosomes and its
proteins.
Our overall aim is to increase the structural knowledge of the lumenal lysosomal
proteins and their transport by combining X-ray crystallography, structural and proteomic analysis, and cell biology. We seek to understand the structural basis of the
lysosomal protein stability and function in low pH as well as their lysosomal targeting. The data will be collected from the overall structural analysis, as well as by studying three structurally novel lysosomal proteins. The hypothesis on the lysosomal
protein recognition will be tested on a glycosidase hydrolase family model system.
Structural knowledge so derived can be directly used to stabilise industrial targets with similar folds and to the design of more suitable ERT-proteins, ones with
better life time in patients or increased crossing rate for the blood-brain barrier. It
benefits individuals suffering from lysosomal storage disorders as it allows design of
improved LSD therapies, as well as to choose between ERT and chaperone therapy.
Studies of individual lysosomal proteins will increase the understanding of the essentials of lysosomal metabolism and the inherited diseases caused by mutations in
their genes. Ultimately, our studies aim to uncover the molecular basis of formation
and maintenance of the hydrolytic lysosomal activity essential in all tissues.
Koutsioulis D, Lyskowski A, Mäki S, Guthrie E, Feller G, Bouriotis V, Heikinheimo P. Coordination sphere of the third metal site is essential to the activity and metal selectivity of alkaline
phosphatases. Protein Science. 2010; 19(1): 75–84.
Kuokkanen E, Smith W, Mäkinen M, Tuominen H, Rantanen M, Jokitalo E, Tollersrud O-K, Cacan R, Duvet S, Berg T, Heikinheimo P. Characterisation and subcellular localisation of human
neutral class II a-mannosidase. Glycobiology. 2007; 17: 1084–1093.
Oksanen E, Ahonen AK, Tuominen H, Tuominen V, Lahti R, Goldman A, Heikinheimo P. A complete structural description of the catalytic cycle of yeast pyrophosphatase. Biochemistry.
2007; 46: 1228–1239.
Wang E, Koutsioulis D, Leiros H-K, Andersen OA, Bouriotis V, Hough E, Heikinheimo P. Structure of alkaline phosphatase from the antarctic bacterium TAB5. J. Mol. Biol. 2007; 366:
1318–1331.
Sbaragli M, Bibi L, Pittis G, Balducci C, Heikinheimo P, Ricci R, Antuzzi D, Parini R, Spaccini L,
Bembi B, Beccari T. Identification and characterisation of novel mutations in Italian patients
with a-mannosidosis. Hum Mutat. 2005; 25: 320–324.
PI Pirkko Heikinheimo
Miami USA, 1997, University of Turku
Finland, 1998; University of Tromsø
Norway 1999–2003
Professor II in NorStruct, University of
Tromsø, Norway, 2005–2006
www.biocenter.helsinki.fi/bi/xray/pirkko
Email: pirkko.heikinheimo@helsinki.fi
Group members
Postdoctoral fellow: Chiara Bruckmann
Graduate students: Heidi Repo,
Elina Kuokkanen
Technician: Seija Mäki
Undergraduate student: Johanna Troberg
NMR studies of larger proteins
by new labelling technology
 Development
of protein ligation and segmental isotopic labeling
to enhance NMR analysis of multi-domain, membrane and transient
protein complexes
S tructural biology increasingly targets larger and more complex systems in
order to fully understand biological functions of a biomolecule. Since bimolecular
function is intimately coupled with changes in structural organization, it is essential
to quantitatively analyze the three-dimensional structures and their dynamics. Nuclear magnetic resonance (NMR) spectroscopy offers unique opportunities to analyze
both high-resolution three-dimensional structures of biomolecules and their dynamics in both near physiological and physiological conditions. NMR analysis of larger
systems has, however, two major obstacles that are line broadening of NMR signals
reducing signal-to-noise ratios and the increased complexity of NMR spectra making NMR analysis difficult and time-consuming. Even though transverse-relaxation
optimized NMR spectroscopy (TROSY) has alleviated the line-broadening problem of
larger systems, the increased number of atoms in large systems (>30 kDa) inherently
increases signal overlaps and remains problematic even with extravagant ultra-high
field magnets.
Our group focuses on developing new labeling technology for structural biology,
particularly for reducing the complexities of NMR spectra of larger proteins. In the
past years, we have advanced protein ligation technology based on protein splicing
by further understanding the mechanism and by applying protein-engineering approaches. Especially, we developed a robust segmental isotopic labeling approach
with which stable isotopes can be incorporated into a specific region of a protein.
This approach not only significantly simplifies NMR spectra but also enables us to
apply sophisticated triple-resonance NMR experiments. By advancing the technologies even further, we are aiming to understand structure-function relationships of
larger protein systems that have been difficult to analyze, which include large multidomain proteins containing recurring modular domains, proteins with intrinsically
disordered regions, transient complexes, and membrane proteins.
PI Hideo Iwai
Dr. sc. nat. 1998, ETH-Zürich,
Switzerland
Zürich, Switzerland, 1998–2003
Assistant Professor, University of
Saskatchewan, Canada, 2003–2005
www.biocenter.helsinki.fi/bi/iwai
Email: hideo.iwai@helsinki.fi
Group members
Postdoctoral fellow: Gerrit Volkmann
Graduate student: Jesper Skøttegaard
Øemig
Undergraduate students: Sesilja Aranko,
Mikael Kuoppala
Aranko AS, Züger S, Buchinger E, Iwaï, H. In vivo and in vitro protein ligation by naturally occurring and engineered split DnaE inteins. PLoS One 2009; 4: e5185.
Busche AEL, Aranko AS, Talebzadeh-Farooji M, Bernhard F, Dötsch V, Iwaï, H Segmental isotopic labelling of a central domain in a multi-domain protein by protein trans-splicing using
only one robust DnaE intein. Angew Chem Int Edit. 2009; 48: 6128–6131.
Oeemig JS, Aranko AS, Djupsjöbacka J, Heinämäki K, Iwaï H. Solution structure of DnaE intein
from Nostoc punctiforme: Structural basis for the design of a new split intein suitable for sitespecific chemical modification. FEBS lett. 2009; 583: 1451–1456.
Muona M, Aranko AS, Iwai H. Segmental isotopic labelling of a multi-domain protein by protein ligation using protein trans-splicing. ChemBioChem. 2008; 9: 2958–2961.
Züger S, Iwai H. Intein-based biosynthetic incorporation of unlabeld protein tags into isotopically labeled proteins for NMR studies. Nat. Biotechnol. 2005; 3: 736–740.
Protein Chemistry Research Group
 Proteomics
and protein chemistry approaches to characterize
activation of innate immunity, Alzheimer astrocytosis, Lactobacillus
probiotic functions, and host-microbe interactions and mutational
mechanisms in Streptococcus and Staphylococcus infections
T he Protein Chemistry Research Group was established in June 1982 at the
Recombinant DNA Laboratory, and has been a part of the Institute of Biotechnology since 1989. The goal of the laboratory has been from the beginning to adopt,
develop, and perform protein chemistry and proteomics analyses to be used in its
own research projects as well as in collaborative projects with academic and industrial partners.
The laboratory is well equipped for modern protein and peptide analysis, including instruments for 1D- and 2D- electrophoresis, chromatography with all separation
parameters down to nanoscale analyses and mass spectrometry. For mass spectrometry a MALDI-TOF/TOF (Bruker Ultraflex) instrument as well as two nanoLC-ESI-QTOF (Q-Tof, Micromass and QStar Elite, Applied Biosystems) instruments are available.
During 2009 we have performed research on the following projects: “Proteomics to
characterise activation of innate immunity”, “Pathogenesis of astrocytosis in Alzheimer’s disease“, “From genomes to probiotic functions: stripping Lactobacillus rhamnosus using expression proteomics, host interactomics and immunoproteomics” and
”Host-microbe interactions and mutational mechanisms in Streptococcus and Staphylococcus infections”. In our proteomics projects we utilize both traditional gel-based
proteomics and newer, non-gel based where both protein identification and quantification is based on mass spectrometry data. We have also focused on developing
new software tools that are needed for efficient proteomic data analysis.
In addition to our own research, we serve also as a Core Facility in protein chemistry and have performed a large number of collaborative protein chemical and proteomics related analyses with other academic as well as industrial groups. These
analyses include e.g. identification of proteins, analysis of protein posttranslational
modifications, confirmation of the identity and structure of produced recombinant
proteins and mass spectrometric de novo sequencing of unknown proteins for e.g.
cloning purposes.
PI Nisse Kalkkinen
PhD 1981, University of Helsinki
Postdoctoral research at Karolinska
institutet, Stockholm, Sweden, various
periods
PI at the Recombinant DNA Laboratory,
www.biocenter.helsinki.fi/bi/protein
Email: nisse.kalkkinen@helsinki.fi
Group members
Senior scientists: Tuula Nyman,
Kirsi Savijoki
Postdoctoral fellows: Johanna Koponen,
Minna Korolainen, Tiina Öhman
Graduate students: Niina Lietzén,
Juho Miettinen, Pia Siljamäki
Technicians: Elina Ahola-Iivarinen,
Marko Hukka, Gunilla Rönnholm
Undergraduate student: Pia Siljamäki
Koskenniemi K, Koponen J, Kankainen M, Savijoki K, Tynkkynen S, de
Vos W, Kalkkinen N, Varmanen P. Proteome analysis of Lactobacillus
rhamnosus GG using 2-D DIGE and mass spectrometry shows differential protein production in laboratory and industrial-type growth
media. J Proteome Res. 2009; 8 (11):4993−5007.
Poutanen M, Varhimo E, Kalkkinen N, Sukura A, Varmanen P, Savijoki
K. Two-dimensional difference gel electrophoresis analysis of Streptococcus uberis under mutagenesis-inducing ciprofloxacin challenge. J
Proteom Res. 2009; 8(1): 246−55.
Salmi J, Nyman TA, Nevalainen O, Aittokallio T. Filtering strategies for
improving protein identification in high throughput MS/MS studies.
Proteomics. 2009; 9: 848−60.
Öhman T, Rintahaka J, Kalkkinen N, Matikainen S, Nyman TA. Actin
and RIG-I/MAVS signaling components translocate to mitochondria
upon influenza A virus infection of human primary macrophages. J
Immunol. 2009; 182(9): 5682−92.
Savijoki K, Alvesalo J, Vuorela P, Leinonen M, Kalkkinen N. Proteomic
analysis of Chlamydia pneumoniae-infected HL cells reveals extensive
degradation of intermediate filament and microtubule proteins.
FEMS Immunol Med Microbiol. 2008; 54(3): 375−84.
Suokko A, Poutanen M, Savijoki K, Kalkkinen N, Varmanen P. ClpL
is essential for induction of thermotolerance and is potentially part
of the HrcA regulon in Lactobacillus gasseri. Proteomics. 2008; 8(5):
1029−1041.
Finnish Biological NMR Center
 NMR
methodology development, structure, dynamics and interactions
of proteins with focus on transient structures and interactions
 NMR methodology development
N MR stands as a unique technique amongst all biophysical tools enabling
studies of biomolecular structures at atomic resolution in solution while simultaneously providing also site-specific data on dynamics and molecular interactions
that regulate life at the molecular level. Our group seeks to understand protein
function through characterization of structure, dynamics and interactions in solution. We mainly focus on proteins and molecular systems whose structures or interactions are dynamic and transient i.e. systems that are difficult to study with the
X-ray crystallography.
We boost our efforts in structural and functional studies of biomolecules by participating strongly in NMR method development. We aim to advance and disseminate routines which help to obtain more information with reduced time and effort.
Novel assignment strategies and hence new probes developed e.g. for epitope mapping, have had key role in studies of several proteins.
Together with our collaborators, we have performed structural and functional
studies of proteins involved in the actin cytoskeleton regulation, cell wall synthesis
and maintenance in S. aureus, signal transduction in T cell activation, neuroprotective mechanisms in dopaminergic neurons. Twinfilin (Twf), a member of ADF-H family, participates in the regulation of actin. It is composed of two ADF-H domains
connected by a long linker. We solved the structure of the C-terminal domain of Twf,
which deviated from G-actin binding proteins, but instead showed high similarity
to cofilin. This suggested, and was later demonstrated, that TwfC possesses similar
depolymerization and severing activities as cofilin. In addition, both domains of Twf
are required for capping the filament barbed end albeit domains can be swapped
without losing this activity. Eps8 mediates downstream signaling by serving as a direct substrate of EGFR. Eps8 has a central role in Rac GTPase activation through its
association with Abi1. Initially SH3 domains were classified as a PxxP motif binding
proteins but recent studies have revealed that the specificity and cellular functions
of SH3s are far more diverse than earlier anticipated. The SH3 domains of Eps8
family do not bind to canonical PxxP peptides, but instead select targets containing a PxxDY sequence. We have determined the structure of Eps8L1 SH3 domain
in complex with the cytoplasmic tail of CD3e, which reveals the structural basis of
novel PxxDY binding. We aim to understand underlying neuroprotective mechanisms
of novel neurotrophic factors MANF and CDNF in collaboration with Prof. Saarma’s
group, characterize interaction between twinfilin and the heterodimeric capping
protein, and study the roles of SH3 domains in ligand recognition in collaboration
with Prof. Saksela (Haartman Institute).
PI Perttu Permi
PhD 2001, University of Oulu, Finland
Postdoctoral research at NMR laboratory at the Institute of Biotechnology,
2001–2003
Docent 2002, University of Oulu
Head of the Finnish Biological NMR
Center since 2004
Academy Research Fellow since 2009
www.biocenter.helsinki.fi/bi/nmr/permi
Email: perttu.permi@helsinki.fi
Group members
Senior scientist: Raili Seppälä-Lehto
Postdoctoral fellows: Maarit Hellman,
Tero Pihlajamaa, Helena Tossavainen
Graduate students: Olli Aitio,
Vytautas Raulinaitis, Peter Würtz
Technicians: Elina Ahonen, Tuomas
Niemi-Aro
Undergraduate students: Sampo Mäntylahti, Fu Biao
Mäntylahti S, Tossavainen H, Hellman M, Permi P. An intraresidual
i(HCA)CO(CA)NH experiment for the assignment of main-chain
resonances in 15N, 13C labelled proteins. J. Biomol. NMR. 2009; 45:
301−310.
Aitio O, Hellman M, Kesti T, Kleino I, Samuilova O, Pääkkönen K,
Tossavainen H, Saksela K, Permi P. Structural basis of PxxDY motif
recognition in SH3 binding. J. Mol. Biol. 2008; 382: 167−178.
Paavilainen V, Hellman M, Bovellan M, Helfer E, Annila A, Carlier MF,
Permi P, Lappalainen P. Structural basis and evolutionary origin of
actin filament capping by twinfilin. PNAS. 2007; 104: 3113−3118.
Würtz P, Aitio O, Hellman M, Permi P. Simultaneous detection of
amide and methyl correlations using a time-shared NMR experiment:
application to binding epitope mapping. J. Biomol. NMR. 2007; 39:
97−105.
Molecular biophysics
of biological energy transduction
 Real-time
recording using single catalytic enzyme turnover of
events resulting in transmembrane ion translocation
R esearch in the group is focused on understanding processes fundamental
to biological energy conversion. We concentrate on the molecular basis for the
coupling mechanisms through which the energy of an electron transfer turns into
a delocalized transmembrane electric potential. Our main tool is real-time recording
of a single catalytic enzyme turnover, with the goal of following all of the molecular events that result in transmembrane ion translocation. The main emphasis our
group makes is on the understanding of the molecular mechanism of proton pump
functioning.
Belevich NP, Verkhovskaya ML, Verkhovsky MI. Electron transfer in respiratory complexes resolved by an ultra-fast freeze-quench approach. In William S. Allison and Immo E. Scheffler,
editors: Methods in Enzimology. 2009; Vol. 456, Burlington: Academic Press, pp. 75−93
Belevich I, Verkhovsky MI. Molecular mechanism of proton translocation by cytochrome c
oxidase. Antioxid Redox Signal. 2008; 10(1): 130.
Gorbikova E, Belevich I, Wikström M, Verkhovsky MI. The proton donor for O-O bond scission
by cytochrome c oxidase. PNAS. 2008; 105: 10733−10737.
Belevich I, Bloch DA, Belevich N, Wikström M, Verkhovsky MI. Exploring the proton pump
mechanism of cytochrome c oxidase in real time. PNAS. 2007; 104: 2685−2690.
Belevich I, Borisov VB, Verkhovsky MI. Discovery of the true peroxy intermediate in the
catalytic cycle of terminal oxidases by the real-time measurement. J. Biol. Chem. 2007; 282:
28514−28519.
Belevich I, Verkhovsky MI, Wikström M. Proton-coupled electron transfer drives the proton
pump of cytochrome c oxidase. Nature. 2006; 440: 829−832.
PI Michael I. Verkhovsky
PhD 1981, Moscow State University,
Russia
Postdoctoral research at Dept. of
Biophysics, Faculty of Biology, Moscow
State University, 1975–1989; Belozersky
Laboratory of Molecular Biology and
Bioorganic Chemistry, Moscow State
University, 1989–1991; Dept. of Medical
Chemistry, Faculty of Medicine, University of Helsinki, 1991–1996
Acting professor in Medical Chemistry
(changed in 2002 to Physical Biochemistry) University of Helsinki, 1996–2006
www.biocenter.helsinki.fi/bi/biophys/
Email: michael.verkhovsky@helsinki.fi
Group members
Senior scientist: Dmitry A. Bloch
Postdoctoral fellow: Belevich Ilya
Graduate students: Virve Rauhamäki,
Elena Gorbikova
Undergraduate students: Marko Rintanen, Ayubah Ndambanghe Linge
Molecular mechanisms of primary energy
transduction in biology and medicine
 Spectroscopic
and other biophysical techniques to follow
essential electron and proton transfer in cell respiration
 Computational techniques to simulate the dynamics and energetics
of structural fluctuations essential for catalysis
T he life of all aerobic organisms depends on primary energy transduction in
cell respiration. Our research elucidates the molecular mechanisms of oxygen reduction and primary transformation of the liberated energy into an electrochemical
proton gradient, subsequently to be used for the synthesis of ATP, the cells’ energy
currency. An understanding of these essential functions can help in the prevention
and diagnosis of several diseases, and may also be valuable in the design of manmade energy transducers on the nanoscale. Recently, we have applied spectroscopic
and other biophysical techniques to follow essential electron and proton transfer
processes of cell respiration in real time, and computational techniques to simulate
the dynamics and energetics of structural fluctuations essential for catalysis. The results of these combined multidisciplinary efforts have given insight into the mechanism of cell respiration on the atomic level, and further work along these lines will
lead to a fundamental understanding of these processes.
Kaila VRI, Verkhovsky MI, Hummer G, Wikström M. Glutamic acid 242 is a valve in the proton
pump of cytochrome c oxidase. PNAS. 2008; 105: 6255−6259.
Verkhovskaya ML, Belevich N, Euro L, Wikström M, Verkhovsky MI. Real time electron transfer in Complex I. PNAS. 2008; 105: 3763−3767.
Belevich I, Verkhovsky MI, Wikström M. Proton-coupled electron transfer drives the proton
pump of cytochrome c oxidase. Nature. 2006; 440: 829−832.
Rauhamäki V, Baumann M, Soliymani R, Puustinen A, Wikström M. Identification of a histidine-tyrosine cross-link in the active site of the cbb3type cytochrome c oxidase from Rhodobacter sphaeroides. PNAS. 2006; 103: 16135−16140.
Wikström M, Ribacka C, Molin M, Laakkonen L, Verkhovsky M, Puustinen A. Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase. PNAS. 2005; 102:
10478−10481.
PI Mårten Wikström
BI Group Leader and Research Director
of the Program in Structural Biology and
Biophysics since 1999
MD, PhD 1971, University of Helsinki,
Finland
Postdoctoral research at the University
of Amsterdam, The Netherlands (EMBO
fellowship), 1971–1972
Visiting professor in physical biochemistry, University of Pennsylvania, Philadelphia, USA, 1975–1976
Professor of Medical Chemistry since
1983; changed in 2002 to Physical
Biochemistry
EMBO Member, 1985
Academy Professor, 1996–2006
www.biocenter.helsinki.fi/bi/hbg/
Email: marten.wikstrom@helsinki.fi
Group members
Senior scientist: Marina Verkhovskaya
Project researcher: Galina Belevich
Postdoctoral fellow: Ville Kaila
Graduate students: Juho Knuuti, Vivek
Sharma
Technicians: Eija Haasanen, Tarja Salojärvi
Core Facilities
DNA Sequencing and Genomics Laboratory
 Environmental
microbiology and metagenomics in complex
surroundings like soil and the Baltic Sea
 de novo genome sequencing and developing a microarray assay for
monitoring microbes in environmental samples
Sequencing services
The DNA sequencing service is directed to customers from universities, research
institutes and companies. Our services cover a wide area of genomics ranging from
single clone sequencing to de novo whole genome sequencing projects. For the
Sanger sequencing an ABI3130 XL 16-capillary sequencer has been used for small
scale sequencing samples and an ABI3730 48-capillary sequencer for high-throughput sequencing.
In the large scale projects we utilize the state of the art technologies. Our laboratory has been pioneering the next generation sequencing in Finland by obtaining
the Roche 454 machine in 2006. In 2009 we have updated the 454 platform to
the Titanium chemistry with increased read length of up to 400 bp and yield of
300–600x10 6 bp per run. The next gen sequencer repertoire was improved in 2008
by obtaining SOLiD 2. SOLiD has been upgraded twice this year; first to SOLiD 3 and
later to SOLiD 3plus. The machine produces 150x10 6 bp – 300x10 6 bp of sequence
with read length of 50 bp giving out 15–30 Gbp of primary sequence per run. The
SOLiD and 454 platforms are used to sequence samples varying from metagenomics
and transcriptomics to de novo genome sequencing.
Research
In recent years one of our main areas has been de novo genome sequencing. We
have been studying dozens of microbe genomes, some of them also commercially
important (Kankainen et al 2009). The fast development of DNA sequencing technologies has already made it possible, in practice, to sequence genomes of all microbes
one works with. We have several ongoing collaborations in this area of genomics.
We have initiated sequencing a large eukaryotic genome utlizing combination of
454 and SOLiD technologies.
One of our interests is environmental microbiology and the diversity of microbial
communities in complex surroundings like soil and the Baltic Sea. We have been
working on environmental metagenomics using the 454 platform. In conjunction
with these environmental sequencing projects we have been successfully developing
a relatively simple, sensitive and specific microarray assay for monitoring microbes
in environmental samples.
The DNA sequencing technologies evolve very rapidly. Along with the new sequencing techniques novel applications using next gen sequencing are arising with
increasing speed. The services provided will be broadening in the future and the parallel sequencing technologies can be utilized in several approaches like EST sequencing, SNP discovery, sequence capture, SAGE, miRNA libraries and functional genomic
approaches like RNA-seq, methyl-seq and ChIP-seq.
Kankainen M, Paulin L, Tynkkynen S, von
Ossowski I, Reunanen J, Partanen P, Satokari
R, Vesterlund S, Hendrickx APA, Lebeer S,
De Keersmaeker SCJ, Vanderleyden J, Hämä
läinen T, Laukkanen S, Salovuori N, Ritari,
J, Alatalo E, Korpela R, Mattila-Sandholm T,
Lassig A, Hatakka K, Kinnunen KT, Karjalai
nen H, Saxelin M, Laakso K, Surakka A, Palva
A, Salusjärvi T, Auvinen P, de Vos W. Com-
parative genomic analysis of the probiotic
Lactobacillus rhamnosus GG reveals pili that
contains a human mucus-binding protein.
PNAS. 2009; 106:17193−17198.
Greco D, Somervuo P, Di Lieto A, Raitila T,
Nitsch L, Castren E, Auvinen P. Physiology,
pathology and relatedness of human tissues
from gene expression meta-analysis. PLoS
Head of the Unit
Petri Auvinen
Laboratory Director at the Institute since 2008
Postdoctoral research at University of Turku,
Finland 1990–1993, at EMBL, Heidelberg,
Germany, 1993–1996
Senior scientist at the Institute 1996–1999
Personnel
Laboratory engineer: Lars Paulin
Senior scientists: Panu Somervuo (a), Dario
Greco, Jenni Hultman
Graduate students: Edward Alatalo, Rashi Gupta
(c, part of the year), Kaisa Koskinen, Pia Laine,
Miia Pitkäranta, Anu Planken (b), Tuomas Raitila
(d), Jarmo Ritari
Technicians: Paula Collin-Olkkonen,
Päivä Laamanen, Kirsi Lipponen, Lea Merviä,
Matias Rantanen, Eeva-Maria Turkki,
Ritva Rajala, Anu Suoranta, Heli Conqiu.
Undergraduate students: Joni Keto, Kui Qian
a) jointly with a consortia
b) jointly with Mart Saarma
c) jointly with Elja Arjas
d) jointly with Marja-Liisa Hänninen
http://www.biocenter.helsinki.fi/bi/dnagen/
Email: petri.auvinen@helsinki.fi
Biocenter Finland infrastructure: Genome-wide
methods
www.biocenter.fi
One, 2008; 3: e1880. doi:10.1371/journal.
pone.0001880.
Hultman J, Ritari J, Romantschuk M, Paulin
L, Auvinen P. Universal ligation-detectionreaction microarray applied for compost microbes. BMC Microbiol. 2008; 8:237.
Kassinen A, Krogius-Kurikka L, Mäkivuokko
H, Paulin L, Rinttilä T, Corander J, Malinen
E, Apajalahti J, Palva A. The fecal microbiota
of irritable bowel syndrome patients differs
significantly from that of healthy subjects.
Gastroenterology. 2007; 133: 24−33.
Laitinen RAE, Immanen J, Auvinen P, Rudd
S, Alatalo E, Paulin L, Ainasoja M, Kotilainen
M, Koskela S, Teeri TH, Elomaa P. Analysis of
floral transcriptosome uncovers new regulators of organ determination and gene families related to flower organ differentiation
in Gerbera hybrida (Asteraceae). Genome Res.
2005; 15:475−486.
Electron Microscopy and CryoEm Unit
T he Electron Microscopy Unit functions as a central core facility for the
whole of the University of Helsinki. Annually we have 50–80 projects from bio-,
medical and material sciences. About one third of the projects are research collaborations, while the others are on the basis of joint use of instruments and paid services. For new users we provide training for the use of our equipment and guidance
for sample preparation. We organize annually practical courses on EM techniques in
collaboration with VGSB and MBIOT. We have been actively setting up advanced EM
techniques such as electron tomography, correlative light electron microscopy, high
pressure freezing and freeze substitution. We were successful in getting a funding
for a new field emission gun scanning electron microscope from Technology Platform Funding in the National Program of Biocenter Finland.
We encourage everyone to visit our web-pages, where we have collected lot of
information about the instruments, methods and practicalities on using the EM facility. There is also a link to our electronic microscopy reservation system and more
information about our research.
Currently we have three transmission and one scanning electron microscopes.
– FEI Tecnai 12 Transmission electron microscope
– FEI Tecnai F20 field emission gun Transmission electron microscope
– Jeol 1200 EX II Transmission electron microscope
– Zeiss DSM 962 Scanning electron microscope (to be replaced during 2010 with a
new FEG-SEM)
All microscopes are equipped with CCD-cameras, and element analysis can be done
on both microscope types. Both Tecnai microscopes are equipped for cryoEM, and
we have a collection of different holders for room temperature, electron tomography and cryo imaging.
For specimen preparation we have three ultramicrotomes of which one is
equipped for cryosectioning and devices for critical point drying, platinum and carbon coating and glow discharge. For cryopreparation we have a high pressure freezing device, freeze substitution units and a guillotine for preparation of thin vitrified
specimens.
The complete list of instruments including all accessory devises can be found
from our web-pages.
List of methods available:
Plastic embedding
High pressure freezing, freeze-substitution
Pre-embedding immunolabelling
Immunolabelling of cryo-sections (Tokuyasu method)
Immunolabelling of acrylic sections
Cytochemical staining of HRP-tagged proteins or endocytosed HRP
Correlative light electron microscopy
Electron tomography
Negative staining
Specimen preparation for scanning electron microscopy (SEM)
Element analysis (EDX microanalysis)
CryoEM Unit
For details, please see Professor Sarah Butcher’s group under Structural Biology and
Biophysics
http://www.biocenter. helsinki.fi/bi/butcher
Email: sarah.butcher@helsinki.fi
Head of the Unit
Eija Jokitalo
Postdoctoral research at Imperial Cancer
Research Fund, Cell Biology Laboratory, London,
UK, 1997–1999
Researcher at the Institute, 2000–2001
Personnel
Senior scientist: Helena Vihinen
Technicians: Virpi Himanen (until 7.9.2009),
Pirkko Leikas-Lazannyi (until 31.8.2009),
Mervi Lindman, Antti Salminen (since
1.10.2009), Arja Strandell
www.biocenter.helsinki.fi/bi/em
Email: eija.jokitalo@helsinki.fi
Biocenter Finland infrastructure:
Biological Imaging www.biocenter.fil
Säälik P, Padari K, Niinep A, Lorents A,
Hansen M, Jokitalo E, Langel Ü, Pooga M.
Protein delivery with transportans is mediated by caveolae rather than flotillindependent pathways. Bioconjugate Chem.
2009; 20: 877−887.
Ylä-Anttila P*, Vihinen H*, Jokitalo E, Eskelinen E-L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 2009; 5:
1180−1185.
Korhonen L, Hansson I, Maugras C, Wehrle
R, Kairisalo M, Borgkvist A, Jokitalo E, Sotelo
C, Fisone G, Dusart I and Lindholm D. Expression of X-chromosome linked inhibitor
of apoptosis protein in mature purkinje cells
and in retinal bipolar cells in transgenic mice
induces neurodegeneration. Neuroscience.
2008; 156: 515−526.
Mattila PK, Pykäläinen A, Saarikangas J,
Paavilainen VO, Vihinen H, Jokitalo E, Lappalainen P. Missing-In-Metastasis (MIM) and
IRSp53 deform PI(4,5)P2-rich membranes by
an inverse BAR domain like mechanism. J.
Cell Biol. 2007; 176:953−64.
Spuul P, Salonen A, Merits A, Jokitalo E,
Kääriäinen L, Ahola T. Role of the amphipathic peptide of semliki forest virus replicase
protein nsP1 in membrane association and
virus replication. J. Virol. 2007; 81: 872−883.
*equal contribution
Core Facilities
Finnish Biological NMR Center
N ational Biological NMR Center provides the state-of-the-art NMR instrumentation, methodology and expertise for the use of research groups in the
fields of molecular biology, biotechnology and molecular medicine in Finland. The facility houses four high-resolution, top-level NMR spectrometers. The 800 MHz spectrometer is the only one in Finland. Although the facility is specially designed and
equipped for biomolecular NMR research, we can, by using broadband probe-heads,
measure practically any element.
Biomolecular NMR studies are often regarded as structure determination of proteins or protein-ligand complexes. Fortunately, NMR can go far beyond by enabling
studies of features that characterize function of a protein i.e. protein dynamics
in timescales ranging from picoseconds to seconds (domain movements, conformational changes, enzyme kinetics, folding), determination of the binding epitope of a
ligand and localization of the binding interface on a protein also in the case of weak
interaction (Kd ~10 –3). Remarkably, NMR based interaction studies do not require
development of a system specific assay.
The NMR Lab has also equipment for cloning, expression and purification of proteins e.g. PCR, two Äkta FPLC systems, incubator shakers, centrifuges, French Press,
sonicator as well as smaller laboratory equipment.
In addition to NMR equipment, the laboratory also has a JASCO-720 CD spectrometer, and a VP-ITC microcalorimeter for isothermal titration calorimetry.
Head of the Unit
Perttu Permi
BI Group Leader and Laboratory Director
since 2004
PhD 2001, University of Oulu, Finland
Postdoctoral research at NMR laboratory at the
Institute of Biotechnology, 2001–2003
Docent 2002, University of Oulu
Academy Research Fellow since 2009
Personnel
Paid service in spectroscopy: Olli Aitio
Laboratory engineer: Tuomas Niemi-Aro
www.biocenter.helsinki.fi/bi/nmr/permi
Email: perttu.permi@helsinki.fi
Structural Biology
www.biocenter.fi
Equipment
Varian Inova 800 MHz with 63 mm bore, three RF channels with 2H decoupling
capability. Pulsed field gradient capability with Performa X,Y,Z module.
– a 5 mm cryogenically cooled 1H{13C, 15N} probehead with z-axis PFG
– a 5 mm 1H{13C, 15N} probehead with xyz-axis PFGs
– a variable temperature unit
Varian Inova 600 MHz, four RF channels with 2H decoupling capability.
– a 5 mm cryogenically cooled 1H{13C, 15N} probehead with z-axis PFG
– a 5 mm 1H{13C, 15N} probehead with z-axis PFG
Varian Inova 600 MHz, four RF channels with 2H decoupling capability,
– a 5 mm 1H{13C, 15N} probehead with z-axis PFG
– a 5 mm 1H{13C, 31P, 15N} probehead with z-axis PFG
Varian Inova 500 MHz, three RF channels with 2H decoupling capability,
– a 5 mm triple-resonance probehead with z-axis PFG
– a 1H{X} nano-probehead with z-axis PFG
Laboratory has a selection of different probeheads for 500 & 600 MHz spectrometers including 5 & 10 mm broadband probeheads with 1H decoupling.
Nakamura F, Heikkinen O, Pentikäinen OT,
Osborn TM, Kasza KE, Weitz DA, Kupiainen
O, Permi P, Kilpeläinen I, Ylänne J, Hartwig
JH, Stossel TP. Molecular basis of filamin AFilGAP interaction and its impairment in
congenital disorders associated with filamin
A mutations. Plos One 2009; 4:e4928.
Nuutinen T, Tossavainen H, Fredriksson K,
Pirilä P, Permi P, Pospiech H, Syvaoja J. Solution structure of amino terminal domain of
human DNA polymerase e subunit B reveals
homology to C-domains of AAA+ proteins.
Nucleic Acids Res. 2008; 36, 5102−5110.
Rantalainen K, Uversky V, Permi P, Kalkkinen N, Dunker K, Mäkinen K. Potato virus A
genome-linked protein VPg is an intrinsically
disordered molten globule-like protein with
a hydrophobic core. Virology. 2008; 377:
280−288.
Bogachev AV, Bertsova YV, Aitio O, Permi
P, Verkhovshy MI. Redox-dependent sodium binding by the Na(+) translocating
NADH:Quinone oxireductase from Vibrio harveyi. Biochemistry. 2007; 46: 10186−10191.
Nakamura F, Pudas R, Heikkinen O, Permi
P, Kilpeläinen I, Munday AD, Hartwig JH,
Stossel T, Ylänne J. The Structure of the
GPIb-filamin A complex. Blood. 2006; 107:
1925−1932.
Light Microscopy Unit
T he light microscopy unit provides high end microscopy systems together
with training, consultation, support and equipment management services. All
equipment is available to all scientific and commercial users. Larger projects, such
as setting up new imaging and analysis systems and methods, are provided as scientific collaboration. We aim to be a facility for high-end data acquisition with a
wide range of supported applications, and to keep pace with developing imaging
technologies by continuously developing and upgrading our services and instrumentation. As before, our primary goal is to satisfy our customers by offering them well
configured and maintained high end light microscopy systems with support ranging
from basic user training to advanced methods development.
Currently we have two confocal microscopes, a Leica TCS SP2 AOBS with an inverted microscope and a Leica TCS SP5 with an upright microscope. Both systems
are equipped for live cell imaging, further details can be found on our web pages.
In addition Leica TCS SP5 MP SMD multiphoton life time imaging system will be
installed in December 2009.
Other available systems include a Till Photonics live cell wide field TIRF system
and two ChipManTech Cell IQ continuous cell culturing & imaging systems one of
which with three channel fluorescence detection in addition to phase contrast. We
also have three image analysis workstations, one with off line licenses for microscope software, one for Cell IQ data analysis and one with a full Bitplane Imaris
suite and Media Cybernetics Autodeblur deconvolution software. Also backed-up
data storage and cell culture facilities are provided.
Head of the Unit
Kimmo Tanhuanpää
Head of the Unit since 2004
Postdoctoral research at Department of
Molecular Medicine, National Public Health
Institute – KTL Helsinki, 2002–2003 and
Institute of Biotechnology, University of
Helsinki, 2003–2004
Personnel
Technician: Mika Molin
www.biocenter.helsinki.fi/bi/lmu/
Email: kimmo.tanhuanpaa@helsinki.fi
Biological Imaging
www.biocenter.fi
mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol. 2009; 185(2): 323−39.
Perttilä J, Merikanto K, Naukkarinen J, Surakka I, Martin NW, Tanhuanpää K, Grimard V,
Taskinen MR, Thiele C, Salomaa V, Jula A, Perola M, Virtanen I, Peltonen L, Olkkonen VM.
OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects,
regulates cellular lipid metabolism. J Mol Med. 2009; 87(8): 825−35.
Shulga A, Blaesse A, Kysenius K, Huttunen HJ, Tanhuanpää K, Saarma M, Rivera C. Thyroxin
regulates BDNF expression to promote survival of injured neurons. Mol Cell Neurosci. 2009;
42(4): 408−18.
Lyly A, Marjavaara SK, Kyttälä A, Uusi-Rauva K, Luiro K, Kopra O, Martinez LO, Tanhuanpää
K, Kalkkinen N, Suomalainen A, Jauhiainen M, Jalanko A. Deficiency of the INCL protein Ppt1
results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism. Hum Mol
Genet. 2008; 17(10): 1406−17.
Uusi-Rauva K, Luiro K, Tanhuanpää K, Kopra O, Martín-Vasallo P, Kyttälä A, Jalanko A. Novel
interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na+, K+ ATPase
complex. Exp Cell Res. 2008; 314(15): 2895−905.
Core Facilities
Protein Chemistry Core Facility
T he Protein Chemistry Research Group has from its beginning in 1982 served
also as a Core Facility (CF) and presently provides analyses for a large number
of academic and industrial researchers and research groups. The present Core Facility analyses are connected to different kind of protein purifications, identifications
and characterizations by electrophoretic, chromatographic and mass spectromertic
methods. Recently also the number of proteomics related analyses have increased.
The main instrumentation of the Protein Chemistry Research Group and Core Facility consists of:
– 1D- and 2D-gel electrphoretic separation systems with adequate imaging and image analysis software.
– Nine different types of liquid chromatographic systems (HPLC) with different protein and peptide separation parameters and column ID:s ranging from 75 µm to
25 mm.
– An Appled Biosystems Procise 494 HT protein/peptide sequencer for N-terminal
protein and peptide sequencing.
– A MALDI-TOF/TOF mass spectrometer (Ultraflex TOF/TOF, Bruker Daltonics, Germany), two nanoLC-ESI Q-TOF mass spectrometers (Q-TOF1, Micromass, UK and
Applied Biosystems Qstar Elite, Applied Biosystems/Sciex, USA).
Jalasvuori M, Jaatinen ST, Laurinavicius S, Ahola-Iivarinen E, Kalkkinen N, Bamford DH, Bamford JK.The closest relatives of icosahedral viruses of thermophilic bacteria are among viruses
and plasmids of the halophilic archaea. J Virol. 2009; 83(18): 9388−97.
Jørgensen R,Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, Wahlberg
L. Characterization of Meteorin − an evolutionary conserved neurotrophic factor. J Mol Neurosci. 2009; 39(1−2): 104−116.
Lehtonen MT, Akita M, Kalkkinen N, Ahola-Iivarinen E, Rönnholm G, SomervuoP, Thelander
M, Valkonen JPT. Quickly released peroxidase of moss in defence against fungal invaders.
New Phytol. 2009; 183(2): 432−443.
Pietilä MK, Roine E, Paulin L, Kalkkinen N, Bamford DH. Isolation and characterization of HRPV-1, the first described ssDNA virus infecting archaea. Mol. Microbiol.2009; 72(2): 307−319.
Paukku K, Kalkkinen N, Silvennoinen O, Kontula KK, Lehtonen JY. p100 increases AT1R expression through interaction with AT1R 3’-UTR. Nucleic Acids Res. 2008; 36(13): 4474−87.
Head of the Unit
Nisse Kalkkinen
(part time in CF)
PhD 1981, University of Helsinki
Postdoctoral research at Karolinska
institutet, Stockholm, Sweden, various
periods
PI at the Recombinant DNA Laboratory,
Personnel
Senior scientist: Tuula Nyman (part time
in CF)
Technicians: Elina Ahola-Iivarinen, technician (part time in CF); Marko Hukka,
technician (part time in CF); Gunilla
Rönnholm, senior technician (part time
in CF)
Other Protein Chemistry Research Group
members participate part-time in CF
according to the need.
www.biocenter.helsinki.fi/bi/protein
Email: nisse.kalkkinen@helsinki.fi
Biocenter Finland infrastructure: Proteomics and Metabolomics
www.biocenter.fi
Protein Crystallisation Facility
O ur protein crystallisation facility provides low volume crystallisation
service in Finland. We use either commercially available screen setups or design
novel screens for crystal optimisation. Our customers can also order custom built
premixed crystallisation solutions for manual crystallisation. Full crystallisation service includes composition of the crystallisation setup and scheduled imaging of the
experiment for up to four months. The crystallisation droplets are set up using our
Cartesian MicroSys or Douglas Instruments Oryx nanodrop robots, which can use
as little as 100 nl protein per experiment. The small volume is essential in order to
save protein in the projects where protein or its complexes are difficult to isolate.
In addition our Oryx robot can setup experiments under oil for samples which are
sensitive to the air interface or require dedicated seeding experiments. As a result,
the scientists receive images from the crystallisation experiments, which follow the
maturation of the project over time. At any time point the customer can obviously
also pick up the crystallisation plate to mount the crystals for an X-ray experiment.
In future we plan to upgrade our system for dedicated methods on membrane protein crystallisation.
Equipment, purpose
Hamilton STAR, liquid Handling robot
Cartesian MicroSys, nanodrop dispenser
Douglas Instruments Oryx 6, nanodrop dispenser
Exploranova Xtal Focus, for imaging at room temperature
Microlab SWAP robotic arm, and
Thermo Rhombix Imager, for imaging at 4°C
700 GB RAID disk system, data storage
Dedicated network server, for image export to end users.
Koutsioulis D, Lyskowski A, Mäki S, Guthrie E, Feller G, Bouriotis V, Heikinheimo P. Coordination sphere of the third metal site is essential to the activity and metal selectivity of alkaline
phosphatases. Protein Sci. 2010; 19(1): 75–84.
Parkash V, Goldman A. Comparison of GFL-GFRalpha complexes: further evidence relating GFL
bend angle to RET signalling. Acta Cryst 2009; F65, 551−8.
Parkash V, Lindholm P, Peränen J, Kalkkinen N, Oksanen E, Saarma M, Leppänen V M, Goldman A. The structure of the conserved neurotrophic factors MANF and CDNF explains why
they are bifunctional. Protein Eng Des Sel. 2009; 22: 233−41.
Heads of the Unit
Pirkko Heikinheimo,
Adrian Goldman
Personnel
Postdoctoral fellow: Andrzej Lyskowski
Technician: Seija Mäki (50%), Katja Rosti
(50%)
www.biocenter.helsinki.fi/bi/xray/automation
Email: bi-crystallisation@helsinki.fi
Structural Biology
www.biocenter.fi
Promoting Careers at the Institute
Careers at BI
T he Institute of Biotechnology offers exciting positions at
all levels of your research training and career. Here you
will find first class research and state-of-the-art scientific services. As a member of one our groups you will be part of a
young international team, using English as your working language. The atmosphere at BI is stimulating, and a distinct pioneering spirit can be felt among our staff. BI housed on the
Viikki campus with “a touch of life” offers an inspiring home
to about 300 scientists and administrative staff.
BI’s research groups are well funded to support a number of
pre- and post-doctoral positions. There is a strong tradition to
encourage traveling and participation in meetings and courses. BI also participates in organizing international meetings
and courses every year especially within the graduate program
curricula. The Viikki Biocenter Lectures (see Table, page 45) is
a weekly high profile research seminar series organized by the
Viikki Research Group Organization in Molecular Biosciences.
If you come to work at BI, we also recognize your private
needs and try to make relocation as smooth as possible. For
newcomers, there are short-term housing possibilities. Our administrative staff is helpful in your legal requirements including visas, work permits, health insurance and family matters.
Finland is an outstanding country for parent with young kids
with world-class public day-care and education, and Helsinki
offers a range of foreign language schooling options. We are
also very aware that many of our new employees are accompanied by spouses looking for qualified positions, and in some
cases can help secure positions. BI has a program to support
your efforts to learn the local languages and we have several
possibilities for team and personal exercise.
Undergraduate and Master’s Programs
BI offers and excellent surrounding for undergraduate training
on the Viikki campus in collaboration with the University of
Helsinki faculties and the Neuroscience Center. The education
coordinator at the Institute of Biotechnology is Professor
Sarah Butcher. Researchers in the Institute are directly responsible for B.Sc. and M.Sc. training in the Helsinki Region
Biotechnology Educational Programme (HEBIOT), which
has expanded undergraduate training in the fields of developmental biology, virology, and neurobiology to systems biology
and structural biology. HEBIOT is a joint initiative in interdisciplinary education by the University of Helsinki and the Aalto
University and Helsinki School of Economics. In the University
of Helsinki, the Faculties of Biosciences, Agriculture and Forestry, Pharmacy, and Medicine, and the Institute of Biotechnology and the Neuroscience Center participate in education.
The Institute of Biotechnology together with the Neuroscience Center contribute significantly to a International
Master’s Degree Programme in Biotechnology (MBIOT),
which is a collaboration with the Faculty of Biosciences and
the Faculty of Agriculture and Forestry. Within the regions of
their expertise, the cell biotechnology, structural biology and
neurobiotechnology researchers at the Institute are responsible for providing essentially all the courses and training, as
well as supervision of the M.Sc. theses.
Many of the Institute’s researchers also participate in other
undergraduate teaching programs at the University. The active role that the Institute of Biotechnology is taking in basic teaching promotes contact with undergraduate students,
teaching at the cutting edge of research and the possibility of
grooming potential PhD students. Moreover, the group leaders
of the Institute can compete on pedagological grounds when
applying for faculty positions. The Institute’s staff is a valuable
teaching resource, providing highly trained expertise in their
fields which has now been mobilized to promote biotechnology education in the Helsinki metropolitan area.
Students wishing to pursue post-graduate studies can thus
readily join research groups at an early stage in their education and can also participate in the educational programs of
the graduate schools prior to completing their Master’s degrees. There are about 50 undergraduate and master’s students rotating in BI groups and preparing the Master’s theses.
Graduate Training and Graduate Schools
Graduate training within Institute groups and number PhD
graduate programs is a critical element for the success of
the Institute integrating training and research. Graduate students join BI through a number of PhD programs available
both within nationally funded and internationally recognized
graduate programs (termed Graduate Schools) and within the
Faculties of the University of Helsinki. Calls for applications
for funded positions in the graduate programs go out annually
or every other year, with contracts typically lasting 4 years.
There are typically about 80 graduate students from all over
the world working at the Institute
The Finnish Graduate Schools have attracted significant international attention as a model for enabling structured highquality PhD training, and provide an exciting opportunity for
international students warmly welcome within the Institute
groups. Training is nationally coordinated through FinBioNet
– Finnish Graduate School Network in Life Sciences, a national network of graduate schools in biosciences and health sciences (www.finbionet.fi).
The four major nationally funded graduate schools Institute
researchers are affiliated with are:
• Helsinki Graduate School in Biotechnology
and Molecular Biology
Director: Professor Pekka Lappalainen
www.biocenter.helsinki.fi/biotechgs
• Viikki Graduate School in Biosciences (VGSB)
Director: Professor Dennis Bamford
www.biocenter.helsinki.fi/viikkigs
• Finnish Graduate School of Neuroscience (FGSN)
Director: Professor Kai Kaila
www.helsinki.fi/fgsn
• National Graduate School in Informational
and Structural Biology (ISB)
Director: Professor Mark S. Johnson
www. abo.fi/isb
Together with our colleagues from the Faculty of Biosciences,
the Faculty of Science, the Faculty of Pharmacy, and the Faculty of Medicine, we organize lectures and practical courses
for these graduate schools. Annually, researchers at the Institute are involved in the organization of 60–90 ECTS credits
for Ph.D. students.
Post-doctoral Training
Postdoctoral scientists are highly valued at the Institute
demonstrated by the nationally very high ratio of postdocs
to graduate students and with an exceptionally high number
of international postdocs. The Institute recruits postdoctoral
scientists worldwide and offers an excellent environment for
young scientists at a critical point in their careers. The Research Programs organize journal clubs and discussion forums,
and mentoring of postdoctoral students is an acknowledged
responsibility of group leaders. A structured post-doctoral
training program is included in the strategy of the Institute
for 2010–12.
Tenure Track
One of the keys to the success of the Institute of Biotechnology has been the ability to offer independent Group Leader
positions to young scientists with strong track records in the
focus areas of the Institute demonstrated by a successful
postdoctoral period in an international setting. Group Leader
contracts have been renewable 5 year contracts pending successful evaluations by a top-level Scientific Advisory Board and
the Institute Board. During 2009 this model has been developed to further clarify and enhance the attractiveness of the
Group Leader positions, and in the 2010 spring call the Institute will for the first time announce Tenure track positions for
new Group Leaders. Further information is available at www.
biocenter.helsinki.fi/bi/recruit/
Vera Shirokova works as a PhD student in Thesleff lab.
"The question that intrigues me much is how so different tissue and
organs can arise from the same cell source" she says. Irma Thesleff
lab focuses on gene signaling regulating ectodermal organ development and Vera's project concerns the role of very interesting and
almost unknown Foxi genes in development of mammary glands
and hair follicles. Vera finds Institute as a good place to work:
"I really enjoy working at the Institute. The whole scientific process
is excellently organized and the work atmosphere is very pleasant
and research stimulating."
Promoting Careers at the Institute
Graduate and advanced courses given by the researchers of the Institute
Viikki Graduate School in Bioscience courses, spring 2009
Course
ECTS
Time
Viikki biocenter Monday lectures spring 2009
Seminar series (once a week, org. Doc. Jussi Jäntti)
Virus club
Seminar series (once a month, org. Doc. Tero Ahola)
Protein NMR-spectroscopy
(together with Bio and Environmental Sciences)
Lectures (org. Doc. Perttu Permi)
Writing a scientific paper**
Lecture course (org. Prof. Adrian Goldman)
From cell to organism - developmental bioloy*
Lecture course (contact Doc. Tapio Heino)
NGS genomatix workshop**
Workshop (org. Doc. Petri Auvinen, Dr. Dario Greco)
Developmental biology, partctical course*
Practical course (org. Doc. Juha Partanen)
The 2nd finnish cell biology symposium
Symposium (org. Doc. Eija Jokitalo & Doc. Jussi Jäntti)
1
Monday 15.15–16.00
Number of participants
average per lecture
70
0.5
Thursday 16–18
30–40
3
13.1.–3.3
Tuesday 12–16
10
1
2.3, 4.3.,6.3.
25
3
10.3.–22.4.
Mon–Tue 10–12
14.–16.4.
40
4.5.–15.5.
15
7–8.5.
60
4
20
Viikki Graduate School in Bioscience courses, fall 2009
Course
ECTS
Time
Viikki biocenter Monday lectures fall 2009
Seminar series (once a week, org. Doc. Jussi Jäntti)
Virus club
Seminar series (once a month, org. Doc. Tero Ahola)
Double-stranded RNA production for plant biotechnology
Practical course (org. Prof. Dennis Bamford)
Stem cells and organogenesis*
Lecture course (org. Doc. Eija Jokitalo and Doc. Maria Vartiainen)
Post-genomics research methods in microbiology
Lectures and practicals (org. Doc. Petri Auvinen and Doc. Nisse Kalkkinen)
1
Mon 15.15–16.00
average per lecture
70
0.5
Thursday 16–18
30–40
1.5
7.–10.9.
16
3
7.9.–13.10.
20
1/3
7.–12.12
25
ECTS
Time
1
7.–8.3.
100
28.8.
50
ECTS
3
Time
18.3−23.4.
26
10
23.2.−6.3.
5
30.9.−23.10.
3
12.3−6.5.
37
3–4
2.11.−16.12.
113
* Together with MBIOT
** Together with GSBM
Helsinki Graduate School in Biotechnology and Molecular Biology
Course
Protein expression and purification
Lecture and practical course (Org. Juha Saarikangas, GSBM)
The 2nd finnish cell biology symposium
Symposium (org. Doc. Eija Jokitalo andDoc. Jussi Jäntti)
Mart Saarma’s 60th birthday symposium:
Brain development and plasticity in health and disease
Symposium (Org. Institute of Biotechnology, Neuroscience Center,
FGSN and GSBM)
HEBIOT/MBIOT Courses, 2009
Course
Recombination mechanisms
Lecture course (org. Prof. Harri Savilahti)
Advanced laboratory course in cellular biotechnology
Laboratory Course (org. Doc. Eija Jokitalo, Doc. Jussi Jäntti and
Doc. Maria Vartiainen)
Indroduction to structural biology and biophysics
Laboratory course (Org. Prof. Sarah Butcher)
Growth factors and their receptors
Lecture course (org. Prof. Mart Saarma)
Introduction to viruses
Lecture course (org. Prof. Dennis Bamford)
Viikki Biocenter Lectures, spring 2009
Organised by Doc. Jussi Jäntti, Institute of Biotechnology
Mitochondrial dysfunction and global lipid
homeostasis
Prof. Anu Wartiovaara, Research Programme of Molecular
Neurology, Biomedicum, University of Helsinki, Finland
(Host: Jussi Jäntti)
Coding, non-coding and nonsense-coding
transcription of the human genome
Prof. Torben Heick Jensen, Centre for mRNP Biogenesis
and Metabolism, Department of Molecular Biology,
University of Aarhus, Denmark (Host: Mikko Frilander)
Regulation of inflammation by the nervous
system
Prof. Heikki Rauvala, Neuroscience Center, University of
Helsinki, Finland (Host: Mart Saarma)
Structure and mechanism of ABC transporters
Prof. Kaspar Locher, Institute of Molecular Biology and
Biophysics, ETH Zurich, Switzerland (Host: Hideo Iwai)
Problems and Potential of academic Drug
Discovery
Prof. John Lazo, Drug Discovery Institute,
University of Pittsburg, USA, (Host: Arto Urtti)
Susceptibility to common cancers:
genetic and epigenetic contributions
Prof. Päivi Peltomäki, Department of Medical Genetics,
University of Helsinki, Finland (Host: Jussi Jäntti)
Biogenesis of the Golgi apparatus
Prof. Graham Warren, Max F. Perutz Laboratories GmbH,
Vienna University, Austria (Host: Eija Jokitalo)
Energy capture by cell respiration
Prof. Mårten Wickström, Institute of Biotechnology,
Integration of light signals controlling plant
development in fluctuating environments
Prof. Jorge Casal, Institute for Agricultural Plant
Physiology and Ecology, University of Buenos Aires,
Argentina (Host: Pedro Aphalo )
The molecular complexity of leukocyte adhesion
Prof. Carl Gahmberg, Division of Biochemistry,
Department of Biological and Environmental Sciences,
System survey of endocytosis by functional
genomics and quantitative multi-parametric
image analysis
Prof. Marino Zerial, The Max Planck Institute of Molecular
Cell Biology and Genetics, Dresden, Germany
(Host: Petri Auvinen)
Evolutionary conservation of sleep regulation at
the molecular and circuit levels
Prof. Leslie Griffith, Brandeis University,
Massachusetts, USA (Host: Tapio Heino)
Heat shock transcription factors at a crossroad
between stress and development
Prof. Lea Sistonen, Turku Centre for Biotechnology,
University of Turku and Abo Akademi University, Finland
(Host: Jussi Jäntti)
The role of the exocyst complex in polarized
exocytosis and cell migration
Prof. Wei Guo, Department of Biology,
University of Pennsylvania, USA (Host: Jussi Jäntti)
A structural mechanism for coordinating
ligand binding by integrins with attachment
to the cytoskeleton
Prof. Timothy Springer, Department of Pathology,
Harvard Medical School and CBR Institute for Biomedical
Research, Inc., Boston, USA (Host: Carl Gahmberg)
The program is available at www.biocenter.helsinki.fi/
Time
19.1.
Seeing begets perceiving:
Insights from direct imaging of protein inter
actions and modifications in living cells
Prof. Tom Kerppola, Department of Biological Chemistry,
Howard Hughes Medical Institute, University of
Michigan, Ann Arbor, USA (Host: Osamu Shimmi)
Phosphate starvation signalling and novel small
RNAs in plants
Prof. Javier Paz-Ares, Centro Nacional de BiotecnologiaCSIC, Madrid, Spain (Host: Yrjö Helariutta)
18.5.
25.5.
26.1.
Viikki Biocenter Lectures, fall 2009
2.2.
9.2.
23.2.
2.3.
9.3.
16.3.
23.3.
30.3.
6.4.
20.4.
27.4.
4.5.
11.5.
LKB1 modulates TGFß signaling and the actin
cytoskeleton
Prof. Tomi Mäkelä, Institute of Biotechnology,
Cell-to-cell communication in plants
Prof. Yrjö Helariutta, Department of Biological and
Environmental Sciences and Institute of Biotechnology,
University of Helsinki, Finland (Host. Jussi Jäntti)
The plasticity of tyrosine kinases
– a chance for inhibitor’s scaffold diversity
Prof. Leonardo Scapozza, School of Pharmaceutical
Sciences, University of Geneva, Switzerland
Progressive myoclonus epilepsies:
from gene defects to molecular pathogenesis
Prof, Anna-Elina Lehesjoki, Folkhälsan Institute of
Genetics, Department of Medical Genetics and Neuroscience Center, University of Helsinki, Finland
Evolution of dispersal in the Glanville fritillary
butterfly: from molecules to landscapes
Prof. Ilkka Hanski, Department of Biological and Environmental Sciences, University of Helsinki, Finland (Host:
Jussi Jäntti)
Neuronal network activity in the developing
cortex
Prof. Kai Kaila, Department of Biological and
Environmental Sciences and Neuroscience center,
Regulation of transport from early-to-late
endosomes
Prof. Anne Spang, Biozentrum, University of Basel,
Switzerland (Host: Jussi Jäntti)
OXPHOS by-pass enzymes as therapy for mitochondrial dysfunction
Prof. Howard Jacobs, Institute of Medical Technology,
University of Tampere, Finland (Host: Mårten Wikström)
How old mothers give birth to young daughters:
lessons from yeast on aging and rejuvenation
Prof. Yves Barral, Institute of Biochemistry, ETH Zurich,
Switzerland (Host: Jussi Jäntti)
Darwin’s laws of correlation of growth
– 150 years later
Prof. Jukka Jernvall, Institute of Biotechnology,
Super-resolution (STED microscopy) investigation
of synaptic vesicle recycling
Dr. Silvio Rizzoli, European Neuroscience Institute,
Göttingen, Germany
Protein phosphatase 2A (PP2A) as a human
tumor suppressor
Jukka Westermarck, Centre for Biotechnology,
University of Turku and Åbo Akademi (Host: Jussi Jäntti)
Structure and metabolism of bacterial cell wall
peptidoglycan
Dominique Mengin-Lecreuxl, Université Paris-Sud, Institut
de Biochimie et Biophysique Moléculaire et Cellulaire and
CNRS, Orsay Cedex, France (Host: Marko Virta)
Time
21.9.
28.9.
5.10.
12.10.
19.10.
26.10.
2.11.
9.11.
16.11.
23.11.
30.11.
7.12.
14.12.
Administration
The Board of the Institute
April 1, 2008–March 31, 2011
Chairman
Professor Esko Ukkonen
Chairman starting from March 18, 2009
(Department of Computer Science,
Faculty of Science)
Members
Academy Professor Lauri Aaltonen
Vice Chairman (Haartman Institute,
Faculty of Medicine)
Professor Kielo Haahtela
(Department of Biosciences, Faculty of
Biological and Environmental Sciences)
Professor Kai Kaila
(Department of Biosciences, Faculty of
Biological and Environmental Sciences)
PhD, Academy Research Fellow
Marja Mikkola (Institute of Biotechnology;
representative of staff)
Research Technician Miika Palviainen
(Institute of Biotechnology;
representative of staff)
Research Professor Merja Penttilä
(Technical Research Centre of Finland)
Professor Vieno Piironen
(Department of Food and Environmental
Sciences, Faculty of Agriculture and
Forestry)
MD, PhD, CEO Markku Jalkanen
(Faron Pharmaceuticals Ltd.;
member starting from March 18, 2009)
Director
Professor Tomi P. Mäkelä, MD, PhD.
Director Mäkelä’s five-year term started
on July 1, 2009.
Acting Director from January 1 to June 30,
2009 Professor, Research Director Irma
Thesleff.
Administration Director
Arto Halinen, M.Pol.Sc.
The members of the Scientific
Advisory Board for the years
2006–2010
Chairman
Professor Jonathan Knowles
(F. Hoffman – La Roche Ltd.,
Basel, Switzerland)
Members
Dr. Marius Clore,
Chief of Protein NMR Section,
Laboratory of Chemical Physics, NIDDK,
National Institutes of Health, USA
Professor Urban Lendahl,
Karolinska Institute, Stockholm, Sweden
Professor Ralf F. Pettersson,
Ludwig Institute of Cancer Research,
Stockholm, Sweden
Dr. Pernille Rorth,
Senior Principal Investigator,
Temasek Life Sciences Laboratory (TLL),
National University of Singapore,
Singapore
Professor Kai Simons,
Max Planck Institute of Molecular Cell
Biology and Genetics, Dresden, Germany
Professor Joan A. Steitz,
Sterling Professor of Molecular Biophysics and Biochemistry, Howard Hughes
Medical Institute, Yale University, USA
Professor John E. Walker,
Medical Research Council, Dunn Human
Nutrition Unit, Cambridge, UK
Funding and Human Resources
Funding 2009
Total Funding
Paid
services
In 1000 Euros
5 939
423
10 766
488
17 616
State budget funding (UH) *
Performance-based funding (UH)
External project funding
Paid services
Total
Percentage
33.7
2.4
61.1
2.8
100
* Includes basic funding, wage increase funding, and space rents.
UH = University of Helsinki.
Performancebased
funding (UH)
External
project funding
External project funding
Granted (in 1000 Euros)
Academy of Finland
5 487
National Technology Agency
241
Other state organisations
1 173
University of Helsinki/Research grants
229
Biocentrum Helsinki
607
Science foundations
1 645
European Union
1 181
Domestic companies
128
Foreign companies
75
10 766
Total
State budget
(UH)
Percentage
51.0
2.2
10.9
2.1
5.6
15.3
10.0
1.2
0.7
100
Domestic
companies
European Union
Science
foundations
Foreign
companies
Academy
of Finland
Biocentrum
Helsinki
University of Helsinki
/Research grants
National Technology Agency
Other state organisations
Paid Services
Laboratory
DNA sequencing
Electron microscopy
Light microscopy
NMR
Protein analysis
Total
Funding (in 1000 Euros)
238
89
88
11
62
488
Funding and Human Resources
Personnel 2009
Administration
Education
Biocenter
Personnel in person years
Researchers*
Undergraduate students
Laboratory technicians
Administration
Education
Biocenter
Total
Person years
195
23
59
11
3
1
292
Percentage
66.8
7.8
20.4
3.7
1.0
0.3
100
Laboratory
technicians
Researchers
Undergraduate
students
* Including graduate students
PhD’s
Proportion of PhD’s in the category researchers: 47%.
Women
Proportion of women in the category researchers: 48% and in students: 67%.
Proportion of women in the whole staff: 61%.
Foreign researchers
40% of all researchers; from 33 countries.
Administration
Education
Biocenter
Personnel (total)
Researchers*
Undergraduate students
Laboratory technicians
Administration
Education
Biocenter
Total
Number
242
51
85
13
4
1
396
Percentage
61.0
12.9
21.5
3.3
1.0
0.3
100
Laboratory
technicians
Undergraduate
students
Researchers
* Including graduate students in 2009
Undergraduate students in 2009
21 undergraduate students preparing their Master’s thesis.
10 Master’s theses were completed.
Proportions of staff categories (%) in person years since 1992
Researchers*
Undergrad. students
Lab. technicians
Administration
Education
Biocenter
Total
(N)
2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992
66.8 67.6 67.9 66.5 61.3 59.8 61.1 60.9 60.8 61.9 64.3 64.5 66.7 63.1 63.5 63.7 62.7 60.3
7.8 7.0 7.2 8.4 11.4 11.5 10.3 13.1 10.0 9.0 7.5 6.4 7.4 8.4 8.9 4.6 6.6 7.0
20.4 20.6 18.8 18.7 20.4 21.3 19.9 19.2 21.5 21.7 21.1 21.9 19.4 21.0 19.4 22.1 21.8 22.8
3.7 3.5 5.1 5.4 5.9 6.1 6.4 5.4 6.5 6.1 5.7 5.7 4.9 6.3 7.4 8.6 7.9 9.1
1.0 1.0 1.0 1.0 1.0 1.0 1.7 1.2 0.7 0.4 0.6 0.3 0.5 0.6 0.8 1.0 1.0 0.8
0.3 0.3 0.0 0.0 0.0 0.3 0.6 0.2 0.5 0.9 0.8 1.2 1.1 0.6 0.0 0.0 0.0 0.0
100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
(292) (286) (293) (299) (304) (296) (283) (288) (299) (301) (278) (229) (215) (177) (125) (103) (96) (88)
* Including graduate students
Staff members
Principal
Investigators
Annila, Arto
Auvinen, Petri
Bamford, Dennis
Butcher, Sarah
Frilander, Mikko
Goldman, Adrian
Heikinheimo, Pirkko
Helariutta, Yrjö
Hietakangas, Ville 2
Holm, Liisa
Iwai, Hideo
Jernvall, Jukka
Jokitalo, Eija
Jäntti, Jussi Kalkkinen, Nisse
Lappalainen, Pekka
Mäkelä, Tomi 2
Partanen, Juha
Permi, Perttu Pirvola, Ulla
Rivera Baeza, Claudio
Saarma, Mart
Schulman, Alan
Shimmi, Osamu
Thesleff, Irma
Vartiainen, Maria
Verkhovsky, Michael Wikström, Mårten Other Researchers
(including staff scientists,
postdoctoral fellows
and graduate students)
Aalto, Antti
Achim, Kaia
Ahola, Tero
Aitio, Olli
Alatalo, Rauno
Amberg, Carolina Louise 2
Andressoo, Jaan-Olle
Aro, Nina Arumäe, Urmas
Balistreri, Giuseppe
Belevitch, Ilya
Belevitch, Nikolai
Bespalov, Maxim
Bishopp, Anthony
Björkgren, Ida 2
Blokh, Dmitry Arnold
Bruckmann, Chiara
Buivydas, Andrius 2
Casagrande, Enrique 2
Chang, Wei
Chernov, Konstantin
Cingi, Suzan 2
Corfe, Ian
Cvirkaite, Virginija
Degerth, Linda 2
Dettmer, Jan
Dopie, Joseph
Eesmaa, Ave 2
Eldfors, Samuli 2
Elo, Annakaisa
El-Showk, Sedeer Nabil
Euro, Liliya 2
Gao, Yajing 2
Gateva, Gergana 2
Goncalves Campilho, Ana 2
Gorbikova, Elena
Greco, Dario
Gupta, Rashi 2
Happonen, Lotta
Harjunmaa, Enni
Hasygar, Kiran 2
Hattula, Katarina
Helenius, Katja 2
Hellman, Maarit
Hellström, Kirsi 2
Help, Hanna
Hotulainen, Pirta 2
Huet, Guillaume
Hultman, Jenni
Häärä, Otso
Immanen, Juha
Immanen, Satu 2
Jakobson, Maili
Jiang, Miao 2
Joensuu, Merja
Jurvansuu, Jaana Jussila, Maria Ainikki
Juuri, Emma 2
Jäälinoja, Harri 2
Jääskeläinen, Marko
Kaila, Ville2
Kajander, Tommi
Kalendar, Ruslan
Kallijärvi, Jukka
Kankainen, Matti
Katajisto, Pekka 2
Kellosalo, Juho Kirjavainen, Anna
Kivelä, Hanna Knuuti, Juho 2
Koponen, Johanna
Korolainen, Minna
Koskinen, Kaisa
Koskinen, Patrik
Kremneva, Elena
Krupovic, Mart
Kumar, Anmol
Kunnapuu, Jaana
1 worked part-time
2 worked part of the year
3 worked part-time and part of the year
Kuokkanen, Elina
Kuuluvainen, Emilia 2
Laajanen, Kaisa 2
Lackman, Petri
Lahti, Laura
Laine, Heidi M
Lefebvre, Sylvie
Lehesranta, Satu Leo, Jack 2
Leppänen, Satu Lichtenberger, Raffael
Lietzen, Niina
Liljeroos, Lassi
Lind, Essi 2
Lindahl, Maria Lindfors, Päivi 2
Lindholm, Päivi Lioudvig, Anastasia
Llano, Olaya
Lume, Maria
Lyskowski, Andrzej
Magalhaes, Ana Cathia
Makkonen, Maarit Manole, Violeta
Mantela, Johanna 2
Marshall, Pepin
Matsuda, Shinya
Mattila, Jaakko 2
Michon, Frederic
Miettinen, Juho
Mikkola, Marja L
Moisy, Cedric
Moringlane, Denise
Munne, Pauliina
Mähönen, Ari Pekka 2
Mätlik, Kert
Neuvonen, Maarit
Nevalaita, Liina Nieminen, Kaisa 2
Nyman, Tuula
Närhi, Katja
Oemig, Jesper
Oksanen, Esko
Ollila, Saara 2
Ora, Ari-Juha
Palm, Erik
Papale, Davide 2
Parkash, Vimal 2
Patana, Anne-Sisko 2
Paulin, Lars Peltopuro, Paula
Peränen, Johan
Pessa, Heli
Pihlajamaa, Tero
Pispa, Johanna 2
Pitkäranta, Miia
Planken, Anu 2
Pljusnin, Ilja
Pohjala, Leena 2
Poranen, Minna
Poutanen, Marjo 2
Puhka, Maija
Pykäläinen, Anette
Rasila, Tiina 2
Rauhamäki, Virve
Raulinautis, Vytautas
Ravantti, Janne
Renvoise, Elodie 2
Repo, Heidi
Ritari, Jarmo
Roine, Elina
Rosenström, Päivi 1
Runeberg-Roos, Pia
Ruzicka, Kamil
Rämö, Olli Juhani
Saarikangas, Juha
Saarimäki-Vire, Jonna
Saito, Kan 2
Sarin, Leif Peter
Sarkhel, Sanjay
Savijoki, Kirsi
Schultink, Anu Annikki 2
Seitsonen, Jani
Seppälä-Lehto, Raili 2
Serlachius, Eva
Sharma, Vivek 2
Shilov, Dmitri
Shirokova, Vera
Shulga, Anastasia
Sidorova, Yulia
Siljamäki, Pia 2
Sinjushina, Natalia
Skarp, Kari-Pekka
Skwarek-Maruszewska, Aneta 2
Smirnov, Sergei
Spuul, Pirjo
Sulg, Marilin
Suomalainen, Marika 2
Säilä, Laura 2
Ta, Xuan Hung
Tanhuanpää, Kimmo
Tanskanen, Jaakko
Tojkander, Sari
Tossavainen, Helena
Trapina, Ilva 2
Tselykh, Timofei 2
Tummers, Mark
Turunen, Janne
Törönen, Petri
Udd, Lina 2
Ursache, Robertas
Vaahtomeri, Kari 2
Vallenius, Tea 2
Vaten, Anne
Weber, Marion
Verbeeren, Jens
Verkhovskaia, Marina
Vihinen, Helena
Vilen, Silja
Virtanen, Heidi 2
Volkmann, Gerrit 2
Voutilainen, Maria
Wurtz, Peter 2
Yadav, Shri Ram 2
Yang, Ke 2
Yang, Ying 2
Yaniv, Elitsur
Yoshida, Toshiyuki 2
Yu, Liying
Yuan, Qiang
Zeng, Zhao
Zhang, Jing 2
Zhao, Hongxia
Ziedaite, Gabija
Zohdy, Sarah
Öhman, Tiina Österlund, Eija 2
Laboratory
Technicians
Ahlsten, Heli 2
Ahola-Iivarinen, Elina Ahonen, Annakaisa 3
Ahovuo, Elina 1
Bansfield, Danielle 2
Basaran, Zeren 2
Bjerstedt, Lotta 2
Bloschies, Melanie 2
Broberg, Raija
Brueckner, Anne 2
Collin-Olkkonen, Paula
Cox, Jan 2
Grimlowski, Randy 2
Haapasaari, Toni 2
Haasanen, Eija
Haukanniemi, Johanna
Heikkinen, Mari
Heikura-Ovaskainen, Marjo 2
Herpola, Mikko
Himanen, Virpi 2
Hukka, Marko
Hämäläinen, Tuulia Ihamäki, Riitta
Jyrkinen, Sirkka
Kainulainen, Katja
Kemppinen, Terhi 2
Koivunen, Eija
Kokkonen, Outi 2
Korhonen, Sari Kortelainen, Joonas 2
Kärkkäinen, Tarja Laamanen, Päivi Laine, Pia
Laine, Saana 2
Laukka, Mari 2
Laurinmäki, Pasi Leikas-Lazanyi, Pirkko 3
Lindman, Mervi Lipponen, Kirsi Lounela, Olli
Lukka, Anneli
Löflund, Benita Lönnqvist, Ursula
Mattila, Rauli Merviä, Lea 50 | Institute of Biotechnology
Molin, Mika Mäki, Seija
Mäkinen, Merja Mäkinen, Tuukka 2
Narvanto, Anne-Mari
Niemi-Aro, Tuomas
Nyfors, Anna-Liisa
Palviainen, Miika
Peltonen, Marja-Leena
Piranen, Elisa
Rajala, Ritva 1
Rantanen, Lauri Rautavesi, Taru 3
Rehn, Maria Renn, Andrea
2
Rintamäki, Noora 2
Rosti, Katja
Rönnholm, Gunilla
Saeger, Bernhard 2
Salminen, Antti
Salojärvi, Tarja Santalahti, Riikka Savolainen, Katja 2
Savolainen, Raija
Seppälä, Heini 2
Shimmi, Risa
Sjögren, Katja 2
Strandell, Arja Suoranta, Anu
Tarkiainen, Riitta Thomaschik, Hannes 2
Turkki, Eeva-Marja
Tynkkynen, Sari Utriainen, Mira 2
Waidonk, Ann Cathrin 2
Viren, Krista 1
Virtanen, Sofia 2
Wiss, Susanna
Åkerberg, Satu
Undergraduate
Students
Aranko, Aino
Atanasova, Nina 3
Baniya, Bijay 2
Bågman, Anne-Maarit 2
Cederlöf, Sari 2
Chen, Xin 2
Crespo Yanez, Xenia 2
Ellilä, Simo 2
Fu, Biao 2
Hakala, Markku
Hasegawa, Hitomi 2
Helin, Kristel 2
Hietavuori, Suvi 2
Hirvonen, Jonni 2
Jaakkonen, Krista 2
Kontturi, Juha 2
Kovacs, Bianca 2
Kowalski, Maria 2
Kuoppala, Mario 2
Kyyrönen, Marika 2
Latvala, Mervi 2
Linge, Ayubah Ndambanghe 2
Luode, Roosa 2
Matilainen, Olli 2
Merilahti, Johannes 2
Mäkilä, Kerttu 2
Nguyen, Trang 2
Ojala, Teija2
Ojefua, Emmanuel 2
Peled, Nitai 2
Pennino, Annunziata 2
Piccinini, Elisa 2
Pietilä, Tuuli 3
Piras, Giuseppa 2
Puusaari, Johanna 2
Qian, Kui 2
Rajakylä, Eeva
Rappou, Elisabeth 2
Rintanen, Marko 2
Rommi, Maija 2
Rosenqvist, Tero 2
Rysti, Elisa 2
Sahal-Estime, Michelle 3
Sonck, Matti 2
Soni, Shetal 2
Sova, Satu
Syed Basha, Mohammed 2
Troberg, Johanna 2
Virolainen, Sini-Maaria 2
Virta, Matilda 2
Åstrand, Mia 1
Administration
Bjerstedt, Kristiina
Halinen, Arto
Kauko, Hannu
Kaukotie, Petri
Leinonen, Sanna
Lepistö, Maija 2
Mäntymaa, Ville 2
Nieminen, Tommi Oja, Minna Peltomaa, Reijo Salo, Iikka Sankkila-Forsström, Satu
Tossavainen, Atro
Education
/ Graduate Schools
Falck, Sandra
Pajari, Anne-Maria 2
Raulo, Erkki 2
Tienhaara, Anita
Biocentrum
Helsinki
Smahl-El Hamraui, Riitta
Publications
Publications
(Authors from the Institute in bold)
Original articles
1. Airavaara M, Shen H, Kuo CC, Peränen
J, Saarma M, Hoffer B, Wang Y.
Mesencephalic astrocyte-derived
neurotrophic factor reduces ischemic
brain injury and promotes behavioral
recovery in rats. J Comp Neurol.
2009; 515(1): 116–124.
2. Alonen A, Gartman M, Aitio O, Finel
M, Yli-Kauhaluoma J, Kostiainen R.
Synthesis, structure characterization,
and enzyme screening of clenbuterol
glucuronides. Eur J Pharm Sci. 2009;
37(5): 581–587.
3. Annila A, Kuismanen E. Natural hierarchy emerges from energy dispersal.
Biosystems. 2009; 95: 227–233.
4. Annila A., Salthe S. Economies evolve
by energy dispersal. entropy. 2009;
11(4): 606–633.
5. Aranko AS, Züger S, Buchinger E,
Iwaï H. In vivo and in vitro protein
ligation by naturally occurring and
engineered split DnaE inteins. PLoS
One. 2009; 4(4): e5185.
6. Bach CT, Creed S, Zhong J, Mahmassani M, Schevzov G, Stehn J, Cowell
LN, Naumanen P, Lappalainen P,
Gunning PW, O’Neill GM. Tropomyosin
isoform expression regulates the transition of adhesions to determine cell
speed and direction. Mol Cell Biol.
2009; 29(6): 1506–1514.
7. Backlund M, Paukku K, Daviet L,
De Boer RA, Valo E, Hautaniemi S,
Kalkkinen N, Ehsan A, Kontula KK,
Lehtonen JY. Posttranscriptional
regulation of angiotensin II type 1
receptor expression by glyceraldehyde
3-phosphate dehydrogenase. Nucleic
Acids Res. 2009; 37(7): 2346–2358.
8. Berg KA, Lyra C, Sivonen K, Paulin
L, Suomalainen S, Tuomi P, Rapala J.
High diversity of cultivable heterotrophic bacteria in association with
cyanobacterial water blooms. ISME J.
2009; 3(3): 314–325.
9. Bloch DA, Borisov VB, Mogi T,
Verkhovsky MI. Heme/heme redox
interaction and resolution of individual optical absorption spectra of
the hemes in cytochrome bd from
Escherichia coli. Biochim Biophys
Acta. 2009; 1787(10): 1246–1253.
10. Bloch DA, Jasaitis A, Verkhovsky MI.
Elevated proton leak of the intermediate OH in cytochrome c oxidase.
Biophys J. 2009; 96(11): 4733–4742.
11. Bogachev AV, Belevich NP,
Bertsova YV, Verkhovsky MI. Primary steps of the Na+-translocating
NADH:ubiquinone oxidoreductase
catalytic cycle resolved by the ultrafast
freeze-quench approach. J Biol Chem.
2009; 284(9): 5533–5538.
12. Bogachev AV, Bloch DA, Bertsova YV,
Verkhovsky MI. Redox properties of
the prosthetic groups of Na(+)-translocating NADH:quinone oxidoreductase.
2. Study of the enzyme by optical
spectroscopy. Biochemistry. 2009;
48(27): 6299–6304.
18. Elo A, Immanen J, Nieminen K,
Helariutta Y. Stem cell function
during plant vascular development.
Semin Cell Dev Biol. 2009; 20(9):
1097–1106.
19. Euro L, Belevich G, Bloch DA,
Verkhovsky MI, Wikström M,
Verkhovskaya M. The role of the
invariant glutamate 95 in the catalytic
site of Complex I from Escherichia coli.
Biochim Biophys Acta. 2009; 1787(1):
68–73.
20. Euro L, Belevich G, Wikström
M, Verkhovskaya M. High affinity
cation-binding sites in Complex I from
Escherichia coli. Biochim Biophys
Acta.2009;1787(8):1024–1028.
13. Bogachev AV, Kulik LV, Bloch DA,
Bertsova YV, Fadeeva MS, Verkhovsky
MI. Redox properties of the prosthetic groups of Na(+)-translocating
nadh:quinone oxidoreductase. 1.
Electron paramagnetic resonance study
of the enzyme. Biochemistry. 2009;
48(27): 6291–6298.
21. Filén JJ, Filén S, Moulder R, Tuomela
S, Ahlfors H, West A, Kouvonen P,
Kantola S, Björkman M, Katajamaa M,
Rasool O, Nyman TA, Lahesmaa R.
Quantitative proteomics reveals GIMAP
family proteins 1 and 4 to be differentially regulated during human T helper
cell differentiation. Mol Cell Proteomics. 2009; 8(1): 32–44.
14. Busche AE, Aranko AS, Talebzadeh-Farooji M, Bernhard F, Dötsch V, Iwaï H.
Segmental isotopic labeling of a central
domain in a multidomain protein by
protein trans-splicing using only one
robust DnaE intein. Angew Chem Int
Ed Engl. 2009; 48(33): 6128–6131.
22. af Gennäs GB, Talman V, Aitio O,
Ekokoski E, Finel M, Tuominen RK, YliKauhaluoma J. Design, synthesis, and
biological activity of isophthalic acid
derivatives targeted to the C1 domain
of protein kinase C. J Med Chem.
2009; 52(13): 3969–3981.
15. Charoenchaikorn K, Yokomizo T, Rice
DP, Honjo T, Matsuzaki K, Shintaku
Y, Imai Y, Wakamatsu A, Takahashi S,
Ito Y, Takano-Yamamoto T, Thesleff I,
Yamamoto M, Yamashiro T. Runx1 is
involved in the fusion of the primary
and the secondary palatal shelves.
Dev Biol. 2009; 326(2): 392–402.
23. Greco D, Volpicelli F, Di Lieto A, Leo
D, Perrone-Capano C, Auvinen P,
di Porzio U. Comparison of gene expression profile in embryonic mesencephalon and neuronal primary
cultures. PLoS One. 2009; 4(3):e4977.
16. Chen Y, Cai H, Pan J, Xiang N, Tien
P, Ahola T, Guo D. Functional screen
reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7
methyltransferase. PNAS 2009; 106(9):
3484–3489.
17. Coleman SK, Möykkynen T, Jouppila
A, Koskelainen S, Rivera C, Korpi ER,
Keinänen K. Agonist occupancy is essential for forward trafficking of AMPA
receptors. J Neurosci. 2009; 29(2):
303–312.
24. Hasegawa H, Holm L. Advances and
pitfalls of protein structural alignment.
Curr Opin Struct Biol. 2009; 19(3):
341–348.
25. Heikkinen O, Permi P, Koskela H, Carpén O, Ylänne J, Kilpeläinen I. Solution
structure of the first immunoglobulin
domain of human myotilin. J Biomol
NMR. 2009; 44(2): 107–112.
26. Heikkinen O, Permi P, Koskela H,
Ylänne J, Kilpeläinen I. 1H, 13C and
15N resonance assignments of the
human filamin A tandem immuno
globulin-like domains 16–17 and 18–19.
Biomol NMR Assign. 2009; 3(1):
53–56.
27. Heikkinen O, Seppälä R, Tossavainen
H, Heikkinen S, Koskela H, Permi P,
Kilpeläinen I. Solution structure of the
parvulin-type PPIase domain of Staphylococcus aureus PrsA-implications for
the catalytic mechanism of parvulins.
BMC Struct Biol. 2009; 9: 17.
28. Heikkinen OK, Ruskamo S, Konarev PV,
Svergun DI, Iivanainen T, Heikkinen
SM, Permi P, Koskela H, Kilpeläinen I,
Ylänne J. Atomic structures of two
novel immunoglobulin-like domain
pairs in the actin cross-linking protein
filamin. J Biol Chem. 2009; 284(37):
25450–25458.
29. Heinämäki K, Oeemig JS,
Djupsjöbacka J, Iwai H. NMR
resonance assignment of DnaE intein
from Nostoc punctiforme. Biomol NMR
Assign. 2009; 3: 41–43.
30. Hotulainen P, Llano O, Smirnov
S, Tanhuanpää K, Faix J, Rivera C,
Lappalainen P. Defining mechanisms
of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol. 2009; 185(2):
323–339.
31. Hytönen MK, Grall A, Hédan B,
Dréano S, Seguin SJ, Delattre D,
Thomas A, Galibert F, Paulin L, Lohi H,
Sainio K, André C. Ancestral T-box
mutation is present in many, but not
all, short-tailed dog breeds. J Hered.
2009; 100(2): 236–240.
32. Jalasvuori M, Jaatinen ST, Laurinavicius
S, Ahola-Iivarinen E, Kalkkinen N,
Bamford DH, Bamford JK. The closest
relatives of icosahedral viruses of thermophilic bacteria are among viruses
and plasmids of the halophilic archaea.
J Virol. 2009; 83(18): 9388–9397.
33. Jia J, Maccarana M, Zhang X,
Bespalov M, Lindahl U, Li JP. Lack
of L-iduronic acid in heparan sulfate
affects interaction with growth factors
and cell signaling. J. Biol Chem. 2009;
284 (23):15942–15950.
34. Jokela-Määttä M, Vartio A, Paulin L,
Donner K. Individual variation in rod
absorbance spectra correlated with
opsin gene polymorphism in sand goby
(Pomatoschistus minutus). J Exp Biol.
2009; 212(Pt 21): 3415–3421.
35. Järvinen E, Tummers M, Thesleff I.
The role of the dental lamina in
mammalian tooth replacement.
J Exp Zoolog B Mol Dev Evol. 2009;
312B(4): 281–291.
36. Jørgensen JR, Thompson L,
Fjord-Larsen L, Krabbe C, Torp M,
Kalkkinen N, Hansen C, Wahlberg L.
Characterization of meteorin-an evolutionary conserved neurotrophic
factor. J Mol Neurosci. 2009; 39(1–2):
104–116.
37. Kaila VR, Johansson MP, Sundholm
D, Laakkonen L, Wikström M. The
chemistry of the Cu(B) site in cytochrome c oxidase and the importance
of its unique His-Tyr bond. Biochim
Biophys Acta. 2009; 1787(4): 221–233.
38. Kaila VR, Verkhovsky MI, Hummer
G, Wikström M. Mechanism and
energetics by which glutamic acid 242
prevents leaks in cytochrome c oxidase. Biochim Biophys Acta. 2009;
1787(10): 1205–1214.
39. Kajander T, Sachs JN, Goldman A,
Regan L. Electrostatic Interactions of
Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90:
computational analysis and protein engineering. J Biol Chem. 2009; 284(37):
25364–25374.
40. Kala K, Haugas M, Lilleväli K, Guimera
J, Wurst W, Salminen M, Partanen J.
Gata2 is a tissue-specific post-mitotic
selector gene for midbrain GABAergic
neurons. Development. 2009; 136(2):
253–262.
41. Kankainen M, Paulin L, Tynkkynen
S, von Ossowski I, Reunanen J,
Partanen P, Satokari R, Vesterlund S,
Hendrickx APA, Lebeer S, De Keersmaecker SCJ, Vanderleyden J, Hämäläinen
T, Laukkanen S, Salovuori N,
Ritari J, Alatalo E, Korpela R, MattilaSandholm T, Lassig A, Hatakka K,
Kinnunen KT, Karjalainen H, Saxelin M,
Laakso K, Surakka A, Palva A, Salusjärvi
T, Auvinen P, de Vos WM. Comparative genomic analysis of Lactobacillus
rhamnosus GG reveals pili containing a
human- mucus binding protein. PNAS.
2009; 106:17193–17198.
42. Kardos R, Pozsonyi K, Nevalainen E,
Lappalainen P, Nyitrai M, Hild G. The
effects of ADF/cofilin and profilin on
the conformation of the ATP-binding
cleft of monomeric actin. Biophys J.
2009; 96(6): 2335–2343.
43. Karnani M, Annila A. Gaia again.
Biosystems; 95; (1): 82–87.
44. Karnani M, Pääkkönen K, Annila A.
The physical character of information.
Proc R Soc A. 2009; 465: 2155–2175.
45. Kim YC, Wikström M, Hummer G.
Kinetic gating of the proton pump in
cytochrome c oxidase. PNAS. 2009;
106(33): 13707–13712.
46. Klaavuniemi T, Alho N, Hotulainen P,
Kelloniemi A, Havukainen H, Permi P,
Mattila S, Ylänne J. Characterization
of the interaction between ActininAssociated LIM Protein (ALP) and the
rod domain of alpha-actinin. BMC Cell
Biol. 2009; 10: 22.
47. Kohonen J, Talikota S, Corander J, Auvinen P, Arjas E. A Naive Bayes classifier for protein function prediction. In
Silico Biol. 2009; 9(1-2): 23–34.
48. Kontkanen H, Westerholm-Parvinen
A, Saloheimo M, Bailey M, Rättö M,
Mattila I, Mohsina M, Kalkkinen N,
Nakari-Setälä T, Buchert J. Novel Coprinopsis cinerea polyesterase that hydrolyzes cutin and suberin. Appl Environ
Microbiol. 2009; 75(7): 2148–2157.
49. Koskenniemi K, Koponen J, Kankainen
M, Savijoki K, Tynkkynen S, de Vos
WM, Kalkkinen N, Varmanen P.
Proteome analysis of Lactobacillus
rhamnosus GG using 2-D DIGE and
mass spectrometry shows differential
protein production in laboratory and
industrial-type growth media. J Proteome Res. 2009; 8(11): 4993–5007.
50. Koutsioulis D, Lyskowski A, Mäki
S, Guthrie E, Feller G, Bouriotis V,
Heikinheimo P. Coordination sphere
of the third metal site is essential to
the activity and metal selectivity of
alkaline phosphatases. Protein Sci.
2009; 19(1): 75–84.
51. Krogius-Kurikka L, Kassinen A, Paulin
L, Corander J, Mäkivuokko H, Tuimala
J, Palva A. Sequence analysis of percent
G+C fraction libraries of human faecal
bacterial DNA reveals a high number of
Actinobacteria. BMC Microbiol. 2009;
9: 68.
52. Krupovic M, Ravantti JJ, Bamford
DH. Geminiviruses: a tale of a plasmid
becoming a virus. BMC Evol Biol.
2009; 9: 112.
53. Kukkaro P, Bamford DH. Virus-host
interactions in environments with a
wide range of ionic strengths. Environ
Microbiol Reports. 2009; 1(1): 71–77.
54. Künnapuu J, Björkgren I, Shimmi O.
The Drosophila DPP signal is produced
by cleavage of its proprotein at evolutionary diversified furin recognition
sites. PNAS. 2009; 106: 8501–8506.
55. Laakkonen JP, Mäkelä AR, Kakkonen
E, Turkki P, Kukkonen S, Peränen J,
Ylä-Herttuala S, Airenne KJ, OkerBlom C, Vihinen-Ranta M, Marjomäki
V. Clathrin-independent entry of
baculovirus triggers uptake of E. coli
in non-phagocytic human cells. PLoS
One. 2009; 4(4): e5093.
56. Lanckriet A, Timbermont L, Happonen
LJ, Pajunen MI, Pasmans F, Haesebrouck F, Ducatelle R, Savilahti H, Van
Immerseel F. Generation of single-copy
transposon insertions in Clostridium
perfringens by electroporation of phage
mu DNA transposition complexes.
Appl Environ Microbiol. 2009; 75(9):
2638–2642.
57. Lee HC, Chang SS, Choudhary S, Aalto
AP, Maiti M, Bamford DH, Liu Y.
qiRNA is a new type of small interfering RNA induced by DNA damage.
Nature. 2009; 459(7244): 274–277.
58. Lehtonen MT, Akita M, Kalkkinen
N, Ahola-Iivarinen E, Rönnholm G,
Somervuo P, Thelander M, Valkonen JP.
Quickly-released peroxidase of moss in
defense against fungal invaders. New
Phytol. 2009; 183: 432–443.
59. Leo JC, Goldman A. The immunoglobulin-binding Eib proteins from
Escherichia coli are receptors for IgG
Fc. Mol Immunol. 2009; 46(8–9):
1860–1866.
60. Linder MD, Mäyränpää MI, Peränen
J, Pietilä TE, Pietiäinen VM, Uronen
RL, Olkkonen VM, Kovanen PT, Ikonen
E. Rab8 regulates ABCA1 cell surface
expression and facilitates cholesterol
efflux in primary human macrophages.
Arterioscler Thromb Vasc Biol.
2009; 29: 883–888.
61. Lindström M, Hinderink K, Somervuo P, Kiviniemi K, Nevas M, Chen Y,
Auvinen P, Carter AT, Mason DR, Peck
MW, Korkeala H. Comparative genomic
hybridization analysis of two predominant Nordic group I (proteolytic)
Clostridium botulinum type B clusters.
Appl Environ Microbiol. 2009; 75(9):
2643–2651.
62. Malet H, Coutard B, Jamal S, Dutartre
H, Papageorgiou N, Neuvonen M,
Ahola T, Forrester N, Gould EA, Lafitte
D, Ferron F, Lescar J, Gorbalenya AE,
de Lamballerie X, Canard B. The crystal
structures of Chikungunya and Venezuelan equine encephalitis virus nsP3
macro domains define a conserved
adenosine binding pocket. J Virol.
2009; 83(13): 6534–6545.
67. Mäntylahti S, Tossavainen H, Hellman M, Permi P. An intraresidual
i(HCA)CO(CA)NH experiment for the
assignment of main-chain resonances
in 15N, 13C labeled proteins. J Biomol
NMR. 2009; 45(3): 301–310.
68. Nakamura F, Heikkinen O, Pentikäinen
OT, Osborn TM, Kasza KE, Weitz DA,
Kupiainen O, Permi P, Kilpeläinen I,
Ylänne J, Hartwig JH, Stossel TP.
Molecular basis of filamin A-FilGAP
interaction and its impairment in
congenital disorders associated with
filamin A mutations. PLoS One. 2009;
4(3): e4928.
69. Neuvonen M, Ahola T. Differential
activities of cellular and viral macro
domain proteins in binding of ADPribose metabolites. J Mol Biol. 2009;
385(1): 212–225.
70. Nevalainen EM, Skwarek-Maruszewska A, Braun A, Moser M, Lappa
lainen P. Two biochemically distinct
and tissue-specific twinfilin isoforms
are generated from the mouse Twf2
gene by alternative promoter usage.
Biochem J. 2009; 417(2): 593–600.
71. Nygårdas M, Vuorinen T, Aalto AP,
Bamford DH, Hukkanen V. Inhibition of coxsackievirus B3 and related
enteroviruses by antiviral short interfering RNA pools produced using phi6
RNA-dependent RNA polymerase. J
Gen Virol. 2009; 90(Pt 10): 2468–
2473.
72. Oeemig JS, Aranko AS, Djupsjöbacka J, Heinämäki K, Iwaï H.
Solution structure of DnaE intein from
Nostoc punctiforme: structural basis
for the design of a new split intein
suitable for site-specific chemical
modification. FEBS Lett. 2009; 583(9):
1451–1456.
63. Mattila J, Bremer A, Ahonen L,
Kostiainen R, Puig O. Drosophila
FoxO regulates organism size and
stress resistance through an adenylate
cyclase. Mol Cell Biol. 2009; 29(19):
5357–5365.
73. Orsini L, Wheat CW, Haag CR, Kvist
J, Frilander MJ, Hanski I. Fitness
differences associated with Pgi SNP
genotypes in the Glanville fritillary
butterfly (Melitaea cinxia). J Evol Biol.
2009; 22(2): 367–375.
64. Michon F, Tummers M. The dynamic
interest in topics within the biomedical scientific community. PLoS One.
2009; 4(8): e6544.
74. Pajunen M, Poussu E, Turakainen
H, Savilahti H. Application of Mu in
vitro transposition for high-precision
mapping of protein-protein interfaces on a yeast two-hybrid platform.
Methods. 2009; 49(3): 255–262.
65. Mouhu K, Hytönen T, Folta K,
Rantanen M, Paulin L, Auvinen P,
Elomaa P. Identification of flowering
genes in strawberry, a perennial SD
plant. BMC Plant Biol. 2009; 9: 122.
66. Munne PM, Tummers M, Järvinen E,
Thesleff I, Jernvall J. Tinkering with
the inductive mesenchyme: Sostdc1
uncovers the role of dental mesenchyme in limiting tooth induction.
Development. 2009; 136(3): 393–402.
75. Palgi M, Lindström R, Peränen J,
Piepponen TP, Saarma M, Heino TI.
Evidence that DmMANF is an invertebrate neurotrophic factor supporting
dopaminergic neurons. PNAS. 2009;
106(7): 2429–2434.
76. Parkash V, Goldman A. Comparison
of GFL-GFRalpha complexes: further
evidence relating GFL bend angle to
RET signalling. Acta Crystallogr Sect
F Struct Biol Cryst Commun. 2009;
65(Pt 6): 551–558.
77. Parkash V, Lindholm P, Peränen J,
Kalkkinen N, Oksanen E, Saarma M,
Leppänen VM, Goldman A. The structure of the conserved neurotrophic
factors MANF and CDNF explains why
they are bifunctional. Protein Eng
Des Sel. 2009; 22(4): 233–241.
78. Perttilä J, Merikanto K, Naukkarinen
J, Surakka I, Martin NW, Tanhuanpää K, Grimard V, Taskinen MR,
Thiele C, Salomaa V, Jula A, Perola M,
Virtanen I, Peltonen L, Olkkonen VM.
OSBPL10, a novel candidate gene for
high triglyceride trait in dyslipidemic
Finnish subjects, regulates cellular lipid
metabolism. J Mol Med. 2009; 87(8):
825–835.
79. Pietilä MK, Roine E, Paulin L, Kalkkinen N, Bamford DH. An ssDNA
virus infecting archaea: a new lineage
of viruses with a membrane envelope.
Mol Microbiol. 2009; 72(2): 307–319.
80. Piltonen M, Bespalov MM, Ervasti
D, Matilainen T, Sidorova YA, Rauvala
H, Saarma M, Männistö PT. Heparinbinding determinants of GDNF reduce
its tissue distribution but are beneficial
for the protection of nigral dopaminergic neurons. Exp Neurol. 2009; 219(2):
499–506.
81. Plyusnin I, Holm L, Kankainen M.
LOCP--locating pilus operons in grampositive bacteria. Bioinformatics.
2009; 25(9): 1187–1188.
82. Pohjala L, Alakurtti S, Ahola T, YliKauhaluoma J, Tammela P. Betulinderived compounds as inhibitors of
alphavirus replication. J Nat Prod.
2009; 72(11): 1917–1926.
83. Polianskyte Z, Peitsaro N, Dapkunas
A, Liobikas J, Soliymani R, Lalowski
M, Speer O, Seitsonen J, Butcher S,
Cereghetti GM, Linder MD, Merckel
M, Thompson J, Eriksson O. LACTB is a
filament-forming protein localized in
mitochondria. PNAS. 2009; 106(45):
18960–18965.
84. Poutanen M, Varhimo E, Kalkkinen
N, Sukura A, Varmanen P, Savijoki K.
Two-dimensional difference gel electrophoresis analysis of Streptococcus uberis
in response to mutagenesis-inducing
ciprofloxacin challenge. J Proteome
Res. 2009; 8(1): 246–255.
85. Psencík J, Collins AM, Liljeroos L,
Torkkeli M, Laurinmäki P, Ansink HM,
Ikonen TP, Serimaa RE, Blankenship
RE, Tuma R, Butcher SJ. Structure of
chlorosomes from the green filamentous bacterium Chloroflexus aurantiacus.
J Bacteriol. 2009; 191(21): 6701–6708.
86. Quintero-Monzon O, Jonasson EM,
Bertling E, Talarico L, Chaudhry F,
Sihvo M, Lappalainen P, Goode BL.
Reconstitution and dissection of the
600-kDa Srv2/CAP complex: roles for
oligomerization and cofilin-actin binding in driving actin turnover. J Biol
Chem. 2009; 284(16): 10923–10934.
87. Rantalainen KI, Christensen PA, Hafrén
A, Otzen DE, Kalkkinen N, Mäkinen
K. Interaction of a potyviral VPg
with anionic phospholipid vesicles.
Virology. 2009; 395(1): 114–120.
88. Rasila TS, Pajunen MI, Savilahti
H. Critical evaluation of random
mutagenesis by error-prone PCR protocols, Escherichia coli mutator strain
and hydroxylamine treatment. Anal
Biochem. 2009; 388(1): 71–80.
89. Rauhamäki V, Bloch DA, Verkhovsky
MI, Wikström M. Active site of
cytochrome cbb3. J Biol Chem. 2009;
284(17): 11301–11308.
90. Ritari J, Paulin L, Hultman J,
Auvinen P. Application of a hybridization control probe to increase accuracy
on ligation detection or minisequencing diagnostic microarrays. BMC Res
Notes. 2009; 2:249.
91. Rzadzinska AK, Nevalainen EM,
Prosser HM, Lappalainen P, Steel KP.
MyosinVIIa interacts with Twinfilin-2 at
the tips of mechanosensory stereocilia
in the inner ear. PLoS One. 2009; 4(9):
e7097.
92. Säälik P, Padari K, Niinep A, Lorents
A, Hansen M, Jokitalo E, Langel
U, Pooga M. Protein delivery with
transportans is mediated by caveolae
rather than flotillin-dependent pathways. Bioconjug Chem. 2009; 20(5):
877–887.
93. Saarikangas J, Zhao H, Pykäläinen
A, Laurinmäki P, Mattila PK, Kinnunen PKJ, Butcher SJ, Lappalainen
P. Molecular mechanisms of membrane
deformation by I-BAR domain proteins.
Curr Biol. 2009; 19(2): 95–107.
94. Salmi J, Nyman TA, Nevalainen OS,
Aittokallio T. Filtering strategies for
improving protein identification in
high-throughput MS/MS studies.
Proteomics. 2009; 9(4): 848–860.
95. Sarin LP, Poranen MM, Lehti NM,
Ravantti JJ, Koivunen MR, Aalto
AP, van Dijk AA, Stuart DI, Grimes
JM, Bamford DH. Insights into the
pre-initiation events of bacteriophage
phi 6 RNA-dependent RNA polymerase:
towards the assembly of a productive
binary complex. Nucleic Acids Res.
2009; 37(4): 1182–1192.
96. Satomaa T, Heiskanen A, Mikkola
M, Olsson C, Blomqvist M, Tiittanen
M, Jaatinen T, Aitio O, Olonen A,
Helin J, Hiltunen J, Natunen J, Tuuri T,
Otonkoski T, Saarinen J, Laine J. The
N-glycome of human embryonic stem
cells. BMC Cell Biol. 2009; 2 ;10:42.
97. Schulte D, Close TJ, Graner A, Langridge
P, Matsumoto T, Muehlbauer G, Sato K,
Schulman AH, Waugh R, Wise RP,
Stein N. The international barley
sequencing consortium--at the threshold of efficient access to the barley
genome. Plant Physiol. 2009; 149(1):
142–147.
106.Takatalo MS, Tummers M, Thesleff I,
Rönnholm R. Novel Golgi protein,
GoPro49, is a specific dental follicle
marker. J Dent Res. 2009; 88(6):
534–548.
107. Täubel M, Rintala H, Pitkäranta
M, Paulin L, Laitinen S, Pekkanen
J, Hyvärinen A, Nevalainen A. The
occupant as a source of house dust
bacteria. J Allergy Clin Immunol.
2009; 124(4): 834–40.e47.
98. Sharma V, Kaila VRI, Annila A. Protein folding as an evolutionary process.
Physica A. 2009; 388: 851–862.
108.Tolvanen M, Ojala PJ, Törönen P,
Anderson H, Partanen J, Turpeinen H.
Interspliced transcription chimeras:
neglected pathological mechanism
infiltrating gene accession queries?
J Biomed Inform. 2009; 42(2):
382–389.
99. Shulga A, Blaesse A, Kysenius K, Huttunen HJ, Tanhuanpää K, Saarma
M, Rivera C. Thyroxin regulates BDNF
expression to promote survival of
injured neurons. Mol Cell Neurosci.
2009; 42(4): 408–418.
109.Törönen P, Ojala PJ, Marttinen P,
Holm L. Robust extraction of functional signals from gene set analysis using a generalized threshold free scoring
function. BMC Bioinformatics. 2009;
10: 307.
100.Siletsky SA, Belevich I, Wikström
M, Soulimane T, Verkhovsky MI.
Time-resolved OHEH transition of
the aberrant ba3 oxidase from Thermus
thermophilus. Biochim Biophys Acta.
2009; 1787(3): 201–205.
110.Törönen P, Pehkonen P, Holm L.
Generation of gene ontology benchmark datasets with various types of
positive signal. BMC Bioinformatics.
2009; 10:319.
101.Skwarek-Maruszewska A, Hotulainen P, Mattila PK, Lappalainen P.
Contractility-dependent actin dynamics in cardiomyocyte sarcomeres. J Cell
Sci. 2009; 122(Pt 12): 2119–2126.
102.Smýkal P, Kalendar R, Ford R, Macas J,
Griga M. Evolutionary conserved lineage of Angela-family retrotransposons
as a genome-wide microsatellite repeat
dispersal agent. Heredity. 2009;
103(2): 157–167.
103.Sundström JF, Vaculova A, Smertenko
AP, Savenkov EI, Golovko A, Minina
E, Tiwari BS, Rodriguez-Nieto S,
Zamyatnin AA Jr, Välineva T, Saarikettu
J, Frilander MJ, Suarez MF, Zavialov
A, Ståhl U, Hussey PJ, Silvennoinen O,
Sundberg E, Zhivotovsky B, Bozhkov
PV. Tudor staphylococcal nuclease is an
evolutionarily conserved component of
the programmed cell death degradome. Nat Cell Biol. 2009; 11(11):
1347–1354.
104.Swee LK, Ingold-Salamin K, Tardivel A,
Willen L, Gaide O, Favre M, Demotz S,
Mikkola M, Schneider P. Biological activity of ectodysplasin A is conditioned
by its collagen and heparan sulfate
proteoglycan-binding domains. J Biol
Chem. 2009; 284(40): 27567–27576.
105.Ta HX, Holm L. Evaluation of
different domain-based methods in
protein interaction prediction. Biochem Biophys Res Commun. 2009;
390(3): 357–362.
111. Tuisku P, Pernu TK, Annila A. In the
light of time. Proceedings of the Proc
R Soc A. 2009; 465: 1173–1198.
112. Tummers M, Thesleff I. The importance of signal pathway modulation
in all aspects of tooth development.
J Exp Zoolog B Mol Dev Evol. 2009;
312B(4): 309–319.
113. Tuomela S, Rautajoki KJ, Moulder R,
Nyman TA, Lahesmaa R. Identification of novel Stat6 regulated proteins
in IL-4-treated mouse lymphocytes.
Proteomics. 2009; 9(4): 1087–1098.
114. Turakainen H, Saarimäki-Vire J,
Sinjushina N, Partanen J, Savilahti
H. Transposition-based method for the
rapid generation of gene-targeting
vectors to produce Cre/Flp-modifiable
conditional knock-out mice. PLoS
One. 2009; 4(2): e4341.
115. Uvarov P, Ludwig A, Markkanen
M, Soni S, Hübner CA, Rivera C,
Airaksinen MS. Coexpression and
heteromerization of two neuronal K-Cl
cotransporter isoforms in neonatal
brain. J Biol Chem. 2009; 284(20):
13696–13704.
116. Vermasvuori R, Koskinen J, Salonen
K, Sirén N, Weegar J, Dahlbacka J,
Kalkkinen N, von Weymarn N.
Production of recombinant HIV-1 nef
protein using different expression host
systems: a techno-economical comparison. Biotechnol Prog. 2009; 25(1):
95–102.
117. Voutilainen MH, Bäck S, Pörsti E,
Toppinen L, Lindgren L, Lindholm P,
Peränen J, Saarma M, Tuominen
RK. Mesencephalic astrocyte-derived
neurotrophic factor is neurorestorative
in rat model of Parkinson’s disease.
J Neurosci. 2009; 29(30): 9651–9659.
118. Vukich M, Schulman AH, Giordani
T, Natali L, Kalendar R, Cavallini A.
Genetic variability in sunflower (Helianthus annuus L.) and in the Helianthus
genus as assessed by retrotransposonbased molecular markers. Theor Appl
Genet. 2009; 119(6): 1027–1038.
119. Wright JT, Morris C, Clements SE,
D’Souza R, Gaide O, Mikkola M,
Zonana J. Classifying ectodermal
dysplasias: Incorporating the molecular basis and pathways (Workshop II).
Am J Med Genet A. 2009; 149A(9):
2062–2067.
120.Wu Z, Xuanyuan Z, Li R, Jiang D, Li C,
Xu H, Bai Y, Zhang X, Turakainen H,
Saris PE, Savilahti H, Qiao M. Mu
transposition complex mutagenesis
in Lactococcus lactis-identification
of genes affecting nisin production.
J Appl Microbiol. 2009; 106(1):
41–48.
121. Ylä-Anttila P, Vihinen H, Jokitalo E,
Eskelinen EL. 3D tomography reveals
connections between the phagophore
and endoplasmic reticulum.
Autophagy. 2009; 5(8): 1180–1185.
122. Zhang Y, Tomann P, Andl T, Gallant NM,
Huelsken J, Jerchow B, Birchmeier W,
Paus R, Piccolo S, Mikkola ML, Morrisey EE, Overbeek PA, Scheidereit C,
Millar SE, Schmidt-Ullrich R. Reciprocal
requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling
pathways in hair follicle induction.
Dev Cell. 2009; 17(1): 49–61.
123. Zhao X, Jäntti J. Functional characterization of the trans-membrane domain interactions of the Sec61 protein
translocation complex beta-subunit.
BMC Cell Biol. 2009; 10:76.
124.Ziedaite G, Kivelä HM, Bamford JK,
Bamford DH. Purified membranecontaining procapsids of bacteriophage
PRD1 package the viral genome.
J Mol Biol. 2009; 386(3): 637–647.
125. Öhman T, Rintahaka J, Kalkkinen N,
Matikainen S, Nyman TA. Actin and
RIG-I/MAVS signaling components
translocate to mitochondria upon
influenza A virus infection of human
primary macrophages. J Immunol.
2009; 182(9): 5682–5692.
Reviews and book chapters
1. Belevich NP, Verkhovskaya ML,
Verkhovsky MI. Chapter 4 Electron
transfer in respiratory complexes
resolved by an ultra-fast freeze-quench
approach. Methods Enzymol. 2009;
456: 75–93.
2. Bishopp A, Help H, Helariutta Y.
Cytokinin signaling during root
development. Int Rev Cell Mol Biol.
2009; 276: 1–48.
3. Blaesse P, Airaksinen MS, Rivera C,
Kaila K. Cation-chloride cotransporters
and neuronal function. Neuron. 2009;
61(6): 820–838.
4. Borisov V B, Verkhovsky MI.
26 August 2009, posting date. Chapter
3.2.7, Oxygen as Acceptor. In A. Böck,
R. Curtiss III, J. B. Kaper, P. D. Karp, F.
C. Neidhardt, T. Nyström, Slauch JM,
Squires CL, and Ussery D (ed.),
EcoSal–Escherichia coli and Salmonella: cellular and molecular biology.
http://www.ecosal.org. ASM Press,
Washington, DC.
5. Dettmer J, Elo A, Helariutta Y.
Hormone interactions during vascular
development. Plant Mol Biol. 2009;
69(4): 347–360.
6. Kalendar R, Lee D, Schulman AH.
FastPCR software for PCR primer
and probe design and repeat search.
Genes, Genomes and Genomics.
2009; 3(1): 1–14.
7. Krupovic M, Bamford DH. Does the
evolution of viral polymerases reflect
the origin and evolution of viruses?
Nat Rev Microbiol. 2009; 7(3): 250;
author reply 250. doi:10.1038/
nrmicro2030-c1.
8. Mikkola ML. Controlling the number
of tooth rows. Sci Signal. 2009; 2(85):
pe53
9. Mikkola ML. Molecular aspects of
hypohidrotic ectodermal dysplasia.
Am J Med Genet A. 2009; 149A(9):
2031–2036.
10. Rivera C. Ion Transport. In: Encyclopaedia of neuroscience. Binder
MD, Hirokawa N, Windhorst U (Eds.)
(2009).
11. Saarma M. GFL neurotrophic factors:
receptors, physiology and pharmacology. Encyclopedia of Neuroscience.
2009; 4: 711–720.
12. Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell
AJ, Leroy P, Morgante M, Panaud O,
Paux E, SanMiguel P, Schulman AH
2009. Reply: A unified classification
system for eukaryotic transposable
elements should reflect their phylogeny. Nat Rev Genet, 2009. 10: p276.
doi:10.1038/nrg2165-c4.
13. Ylä-Anttila P, Vihinen H, Jokitalo E,
Eskelinen EL. Monitoring autophagy
by electron microscopy in mammalian
cells. Methods Enzymol. 2009; 452:
143–164.
Other publications
1. Eronen JT, Jernvall J. Hampaiden
evoluutio. Duodecim. 2009;
125(18):2017–2022.
2. Frilander M. J. Kemian Nobel-palkinto
ribosomien rakenteen selvittäjille.
Duodecim. 2009; 125: 2476–2477.
3. Hultman J, Auvinen P. Mikrobiyhteisöjen tutkiminen metagenomiikan
avulla. Natura, 04/2009: 14–18.
PhD Theses
1. Bespalov Maxim (Saarma lab). GDNF
Receptors: Veterans and novices.
Faculty of Biosciences, Department of
Biological and Environmental Sciences,
Division of Genetics, Institute of
Biotechnology, University of Helsinki.
Dissertationes bioscientiarum
molecularium Universitatis
Helsingiensis in Viikki 40/2009.
2. Euro Liliya (Wikström lab).
Electron and proton transfer in
NADH:ubiquinone oxidoreductase
(Complex I) from Escherichia coli.
University of Helsinki. Dissertationes
bioscientiarum molecularium
Universitatis Helsingiensis in
Viikki. 13/2009.
3. Gorbikova Elena (Verkhovsky lab).
Oxygen reduction and proton translocation by cytochrome c oxidase.
Division of Biochemistry, Institute of
Biotechnology, Helsinki Bioenergetics
Group, University of Helsinki. Dissertationes bioscientiarum molecularium Universitatis Helsingiensis
in Viikki 15/2009.
4. Greco Dario (Auvinen lab). Gene
Expression: From microarrays to
functional genomics. Faculty of Biosciences, Department of Biological and
Environmental Sciences, Genetics
Institute of Biotechnology, University
of Helsinki. Dissertationes bioscientiarum molecularium Universitatis
5. Gupta Rashi (Auvinen lab). Methods
to improve gene signal: Application to
cDNA microarrays. Faculty of Science,
Department of Mathematics and Statistics, DNA sequencing and genomics
laboratory, Institute of Biotechnology,
University of Helsinki. Yliopistopaino,
2009.
6. Hultman Jenni (Auvinen lab).
Microbial diversity in the municipal
composting process and development
of detection methods. Faculty of
Biosciences, Department of Ecological
and Environmental Sciences Institute
of Biotechnology, University of Helsinki. Reports from the Department
of Ecological and Environmental
Sciences / University of Helsinki,
Lahti 9.
7. Jaatinen Silja T (Bamford lab). Lipidcontaining icosahedral dsDNA bacteriophages: Entry, exit and structure.
Division of General Microbiology,
Universitatis Helsingiensis in Viikki
10/2009.
8. Kaila Ville R I (Wikström lab). Theoretical studies on coupled electron and
proton transfer in cytochrome c oxidase. Faculty of Biosciences, Department of Biological and Environmental
Sciences, Division of Biochemistry,
9. Kukkaro Petra (Bamford lab).
Characterization of new viruses from
hypersaline environments. Faculty of
Biosciences, Department of Biological
and Environmental Sciences, Institute of Biotechnology, University of
Helsinki. Dissertationes bioscientiarum molecularium Universitatis
10. Leo Jack C (Goldman lab). Structural
and functional studies on trimeric autotransporters. Faculty of Biosciences,
Department of Biological and Environmental Sciences, Genetics, Research
Program in Structural Biology and
Biophysics, Institute of Biotechnology,
32/2009.
11. Lindholm Päivi (Saarma lab). Novel
CDNF/MANF protein family: molecular
structure, expression and neurotrophic
activity. Institute of Biotechnology &
Department of Biological and Environmental Sciences, Division of Genetics,
Universitatis Helsingiensis in Viiki
25/2009.
12. Mattila Jaakko (Puig lab). Regulation
of growth by drosophila foxO transcription factor. Faculty of Biosciences,
13. Nevalainen Elisa (Lappalainen lab).
The biological functions of mouse
twinfilin isoforms. Faculty of Biosciences, Department of Biological
and Environmental Sciences, Genetics,
14. Oksanen Esko (Goldman lab). Enzyme
molecular choreography: studies on
soluble inorganic pyrophosphatases.
Faculty of Science, Department of
Chemistry, Laboratory of Organic
Chemistry, Institute of Biotechnology,
39/2009.
15. Parkash Vimal (Goldman lab).
Neurotrophic factors and their receptors. Faculty of Biosciences, Department of Biological and Environmental
Sciences, Division of Biochemistry,
16. Patana Anne-Sisko (Goldman lab).
The human UDP-glucuronosyltransferases: Studies on substrate binding
and catalytic mechanism. Institute
of Biotechnology, Faculty of Biosciences, Department of Biological and
Environmental Sciences, Biochemistry,
3/2009 .
17. Pummila Marja (Thesleff lab). Role of
Eda and Troy pathways in ectodermal
organ development. Faculty of Biosciences, Department of Biological and
Environmental Sciences, Physiology
Helsingiensis in Viikki. 23/2009.
18. Skwarek-Maruszewska Aneta
(Lappalainen lab). Actin dynamics in
muscle cells. Faculty of Biosciences,
University of Helsinki.
molecularium Universitatis
19. Tselykh Timofey (Mäkelä lab).
Functional analysis of MrpL55, Vig and
Mat1 acting at the crossroad of cell
cycle, transcription and metabolism
regulation. Faculty of Biosciences,
Department of Biological and Environmental Sciences, University of Helsinki.
molecularium Universitatis Helsingiensis in Viikki 29/2009.
20. Virtanen Heidi (Saarma lab).
Structure-function studies of GDNF
family ligand-RET signalling. Faculty of
and Environmental Sciences, Division
of Biochemistry Institute of Biotechnology, University of Helsinki. Dissertationes bioscientiarum molecularium Universitatis Helsingiensis
in Viikki 19/2009.
21. Yu Li-Ying (Saarma lab). Death pathways activated in the neurotrophic
factor-deprived neurons. Faculty of
and Environmental Sciences, Institute of Biotechnology. University of
Helsinki. Dissertationes bioscientiarum molecularium Universitatis
Patents
and patent applications
1. Karelson M, Truve E, Olspert A.
Sarmiento C, Saarma, M. US patent
application WO 2009/060124 A2.
Use of oligonucleotides with modified
bases in hybridization of nucleic acids.
First published 14.05.2009.
2. Penn R, Bespalov M, Peränen
J, Runeberg-Roos P, Saarma M.
Improved Neurturin Molecules.
Serial number: 61/256,352, Filing Date:
30/10/ 2009.
3. Saarma M. Merits A, Karelson, M. US
patent application WO 2009/060122
A2. Use off oligonucleotides with
modified bases as antiviral agents. First
published 14.05.2009.
4. Saarma M, Lindholm P, Voitilainen
M, Peränen J, Tuominen RK, Airavaara
M, Leppänen V-M, Lindahl M,
Andressoo J-O. Neurotrophic factor
MANF and uses thereof. United States
Patent Application 20090282495;
Application Number: 12/433345, Publication Date: 11/12/2009; Filing Date:
04/30/2009.
Institute of Biotechnology
P.O.Box 56, FI-00014 University of Helsinki
Tel. +358 9 1911, fax +358 9 191 39366
www.biocenter.helsinki.fi/bi
E-mail: biotek@helsinki.fi

Institute of Biotechnology – Annual report 2009 University of Helsinki

Transcription

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