Julieta Acevedo

 Julieta Acevedo
‘Study of the role of the molecular oxygen sensor, Fatiga, in the oogenesis
of Drosophila melanogaster’.
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Eric Brooks Research Statement I’m deeply interested in the question of the underlying cytoskeletal dynamics of development. I am especially interested in cilia, given these organelles potent developmental functions. Ciliogenesis is accomplished by the coordinated, bi-­‐directional transport of microtubule-­‐motor driven transport within the axoneme. This transport is facilitated by a set of highly conserved proteins known as the IntraFlagellar Transport (IFT) machinery. While the genetics and biochemistry of IFT are fairly well understood in ciliated eukaryotes, our understanding of the dynamics of this process—especially in vertebrates—has been constrained by our inability to image the process with the requisite temporal and spatial resolution. Using the large axonemes of the embryonic Xenopus epidermis I have directly visualized IFT at the resolution of single IFT trains within the axoneme, and have begun to quantify behaviors. In addition, I have found that the Planar Cell Polarity effector Fuzzy is essential for the appropriated dynamic behaviors of vertebrate IFT. I am currently engaged in better understanding the molecular mechanisms by which Fuzzy modulates IFT dynamics, in addition to expanding the initial analysis of wild-­‐type IFT dynamics. Finally, we are beginning to examine Fuzzy binding-­‐partners, as well as other PCP components for a role in IFT during ciliogenesis. Windows of vulnerability in development: loss of
multidrug efflux in sea urchin pluripotent cells
Joseph P. Campanale
The large number of chemicals in the environment could represent a significant
emerging risk to the health of most embryos. Recent research by the
Environmental Working Group indicate 287 environmental chemicals, including
pesticides, herbicides, heavy metals, DDT and dioxins could be detected in
human umbilical cord blood. These results show that human embryos are
exposed to many chemicals in utero, as are embryos of most other species that
develop in direct contact with the external environment. However, little is known
about how embryos eliminate and/or detoxify chemicals or about specific
windows of chemical vulnerability during development. Although embryos have
potent defenses against environmental stress, many chemicals can act in stage,
species and cell-type specific ways to induce teratology. Using sea urchin
embryos as a model, my recent results indicate that pluripotent stem cells, the
small micromeres, experience a dramatic decrease in a key chemical defense,
ATP-binding cassette (ABC) efflux transport. To understand the causes and
consequences for the loss of protective efflux activity from critical cell types I use
fluorescent efflux transporter substrates to survey the activity of these pumps and
image live sea urchin embryos using confocal microscopy. To understand the
regulation of defensive strategies in embryos my research seeks to: 1)
quantitatively describe the amount and types of efflux transporter activity for a
variety of cell types and the developmental timeline for changes in their activity,
2) assess whether the loss of ABC-transporter activity sensitizes the small
micromeres to known environmental contaminants indicating their relative
vulnerability and 3) to examine whether loss of ABC-transporter activity is part of
a conserved developmental signaling pathway that drives cellular migration by
sensitizing different cells to different developmental chemicals in the embryo.
Yi-Ju Chen
Current research topics
(1) Sequence dependent flexibility of DNA
Certain non-coding DNA sequences are thought to constrain nucleosomal positioning as
a result of their different flexibility from generic sequences. Making use of the lac
operon, we measure the free energy of loop formation of these special sequences by
tethered particle motion.
(2) Bacterial phage λ ejection dynamics
We’re interested in observing the life cycle of bacterial phage in the single cell/single
molecule level. In particular, the real-time observation of the injection process allows us
to quantify the injection dynamics and evaluate various models.
David Gold Diffusing the Cambrian Explosion: A multidisciplinary approach to the
origins of animal life Common understanding of the fossil record suggests that animal bodyplans evolved rapidly during a "Cambrian explosion" about 530 million years ago. But recent discoveries in the Precambrian fossil record, combined with “evo-­‐devo” research on early branching animal lineages has provided a clearer picture of bodyplan evolution. I study the early radiation of animal form by combining developmental and paleontological approaches. My research focuses on the affinities and biomechanics of animals from the Precambrian, and using the moon jellyfish Aurelia aurita as a model system for the evolution of complexity in an early branching animal lineage. This research on A. aurita includes the developmental genetics of neurogenesis, sensory systems, and the role of stem cells in regeneration. Jacob (Jake) Hines Neural development I started my research career as an undergraduate studying central pattern generators in the neonatal rat spinal cord. Aiming to identify neurotransmitter receptors involved in these locomotor networks, I became especially curious about how these circuits were formed. Following these interests, I then completed my graduate studies at the Mayo Clinic studying axon guidance mechanisms. In my thesis work, I discovered that nerve growth cones, the motile tips of axons, can turn away from chemorepellent gradients by breaking the symmetry of adhesion to the extracellular matrix. One way such asymmetry is acquired involves internalizing integrin receptors preferentially on one side of the growth cone. Beyond axonal growth and targeting, I am also interested in how neurons and glia migrate and recognize specific cellular targets in order to build functional circuits. I recently began a Post-­‐
doc in Bruce Appel’s lab at the University of Colorado – Denver. Here, I am learning the zebrafish model and aim to identify mechanisms by which oligodendrocytes, the myelinating cells of the CNS, migrate and wrap axons. I am excited to strengthen my background in developmental biology and hope the MBL experience will deliver new tools and ideas to my research project and others in the lab. Lynn Kee Graduate student, University of Michigan Title of Research: Investigating molecular mechanisms that regulate protein import into primary cilia in mammalian cells Research Summary: My thesis work is focused on primary cilia, which are specialized microtubule-­‐based organelles that protrude from the surface of most vertebrate cells and function as a major signaling center for pathways important for normal cellular development and homeostasis. Disruption of proteins that normally localize and function in cilia results in a range of human diseases collectively termed ciliopathies, including retinal degeneration, polycystic kidney diseases, and obesity. Cilia contain a unique set of cellular proteins, however, the molecular mechanisms by which ciliary proteins gain access to the ciliary compartment are not well understood. My research is focused on characterizing molecular mechanisms that regulate import into the ciliary compartment in mammalian cells. Recently, we demonstrated that the ciliary entry of the ciliary kinesin motor protein KIF17 is regulated by nuclear import components. Specifically, we determined that KIF17 contains a ciliary localization sequence (CLS) that binds to importin-­‐β2 for transit into the cilium where high levels of RanGTP dissociate the complex. My current work is aimed at further characterizing the similarities between nuclear and ciliary import mechanisms. Primary cilia in mammalian cell. A representative image of the Lucas Leclère
Sars International Centre
for Marine Molecular Biology
Thormøhlensgt 55
5008 Bergen, Norway
Phone: +47 55584338
E-mail: Lucas.Leclere@sars.uib.no
Post-doc: Netrin signalling and axon guidance
in the cnidarian Nematostella vectensis
I did my PhD (2005-2008) in the laboratory of the Pr. Michaël Manuel (UMPC, Paris,
France) and studied developmental and evolutionary aspects of sexual reproduction
in hydrozoans (Cnidaria) and ctenophores. Since beginning of 2009, I am post-doc at
the Sars International Centre for Marine Molecular Biology in Bergen (Norway), in the
team of Fabian Rentzsch. I work on some molecular aspects of the embryonic
development of the sea anemone Nematostella vectensis (Anthozoa, Cnidaria). My
research focuses on the Netrin signaling pathways in the sea anemone Nematostella
vectensis. This pathway is involved in diverse bilaterian phyla in axon guidance and
notably in guidance of axons in the central nervous system. Study of this pathway in
a cnidarian is motivated by the fact that cnidarian present molecular components of
this pathway, but lack a central nervous system or unipolar nerve cells. I have cloned
extracellular and transmembrane proteins of this signaling pathway (Netrin, RGM,
Neogenin, Unc5) and investigated expression of these genes by in situ hybridization.
I am currently analyzing function of these genes using injection morpholino antisense
oligonucleotides and RNA in early stages, and by generating transgenic lines in order
to determine protein localization and promoter structure. This study aims at providing
insights into the evolution of this signalling pathway and more generally about
evolution of axon guidance in metazoans.
Chung-­Fan Lee Epigenetic modifications are the heritable and
reversible changes on DNA or histones, which
regulates gene expression without alteration of the
sequence.
I
am
interested
in
DNA
understanding
epigenetic regulations during cancer progression
and
embryonic development.
During my PhD studies, I focused on the roles of
epigenetic modifications in lung cancer and
oncogenic virus. I initiated and carried out my major project about how hNaa10p, a novel
acetyltransferase, promotes lung cancer progression through recruiting DNMT1 to downstream tumor
suppressor genes to repress their expressions (JCI, 2010, August 02). I also participated in the
investigations regarding the modulation of DNMT1 by NNK in lung cancer (JCI, 2010, February 01) and
the functions of chromatin assembly factor 1 (CAF1) in viral life cycle (JBC, 2009 and Cell Research,
2010).
In contrast to the cancer studies, there are still lots unknown about the roles of epigenetic regulation
during early developmental stages. Currently, I began to study this issue by using transgenic animal
model.
Lee, S.-B., Lee, C.-F., Ou, D.-S., Chang, L.-H., Dulal K., Ma, C.-H., Huang, C.-F., Zhu, H., Lin Y.-S.
and Juan, L.-J.. Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2. Cell
Research. (2011, in press)
Lee, C.-F., Ou, S.-C., Lee, S.-B., Chang, L.-H., Lin, R.-K., Li, Y.-S., Upadhyay, A.-K., Cheng, X., Wang,
Y.-C., Hsu, H.-S., Hsiao, M., Wu, C.-W. and Juan, L.-J. (2010) hNaa10p contributes to tumorigenesis by
facilitating DNMT1-mediated tumor suppressor gene silencing. J Clin Inves 120(8):2920–2930.
Lin, R.-K., Hsieh, Y.-S., Lin, P., Hsu, H.-S., Chen, C.-Y., Tang, Y.-A., Lee, C.-F. and Wang, Y.-C.
(2010) The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor
suppressor gene hypermethylation in mice and lung cancer patients. J Clin Invest 120(2):521-32.
Lee, S.-B., Ou, D.S.-C.*, Lee, C.-F.* and Juan, L.-J. (2009) Gene-specific transcriptional activation
mediated by the p150 subunit of the chromatin assembly factor 1. J Biol Chem 284: 14040-9. (* cosecond authors).
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Elasticity of developing embryonic tissue and its influence on early cardiomyocyte beating Stephanie Majkut, Discher Lab, University of Pennsylvania Previous work has demonstrated the effects of cardiomyocyte mechanosensitivity to ECM elasticity on beating physiology of 10 day chick embryo cardiomyocytes[1] and also of neonatal rat cardiomyocytes[2], developmental stages for which the heart mechanics are established and the Young’s modulus is E~10-­‐20 kPa. I am interested in looking at the effects of cardiomyocyte mechanosensitivity throughout development. How are mature cardiac tissue mechanics established, and as these properties change, what role does the effect of extracellular mechanics play in early cardiomyocyte function and differentiation? I use micropipette aspiration to characterize local mechanical properties of embryonic chick heart tissue throughout development. Cardiac tissue stiffens 3-­‐fold from early embryonic tissue by embryonic day two (E2), just after the onset of beating. It continues to stiffen up to 20-­‐fold by E14, reaching approximately neonatal levels. As an example of a non-­‐
fibrous tissue that we do not expect to undergo such rigidification and tissue-­‐scale network behavior, we characterized embryonic brain tissue by micropipette aspiration as well. To identify possible general molecular mechanisms involved in the tissue mechanics, we have done a quantitative mass-­‐spec study of heart and brain tissue at E2, E4, E10. For high molecular weight proteins (100-­‐300 kDa), out of 120 detected proteins, 11 had expression levels that paralleled the rigidity changes across tissues and developmental stages. In particular, E2 heart levels are greater than E2 brain, and levels remain approximately constant in brain during development, but increase in heart. These proteins included primarily cytoskeletal contractile proteins such as myosins and sarcomeric proteins, as well as ion channel proteins important to excitation-­‐contraction coupling. As far as extracellular matrix proteins, we found that Collagen Ia1 and Ia2 identified by Mass-­‐Spec strongly followed the rigidity trends. We are currently analyzing the low molecular weight proteins from these samples and working on better solubilization protocols for ECM proteins. To assess the respective contributions of these proteins to the total tissue mechanics, I perturbed the actomyosin contractility and collagen network using blebbistatin and collagenase treatments, respectively. I find that blebbistatin softens heart tissue by ~30%, and significantly softens brain tissue, possibly to a greater degree. Collagenase significantly softens heart tissue in a dose-­‐dependent manner, but does not significantly soften brain tissue I have used an in vitro system of collagen coated polyacrylamide gels of varying stiffnesses to examine the effects of substrate stiffness on isolated cardiomyocytes. Early cardiomyocyte (E3-­‐
E4) beating magnitude is modulated by an elasticity of 1-­‐2 kPa, close to the physiological tissue elasticity measured by micropipette for tissue at that stage. [1] A. Engler et al. Journal of Cell Science 121: 3794-­‐3802 (2008). [2] J. Jacot, et al. Biophysical Journal 95(7): 3479-­‐3487 (2008). Megan Martik
Gastrulation is a complex orchestration of
movements by cells that are specified early in
development. Live imaging and experimental
techniques allow examination of
morphogenesis at the cellular level in the
optically clear sea urchin embryo. Using timelapse microscopy, our lab has discovered a
new phenomenon that we have termed
“telescoping” which contributes significantly to
gut elongation. During gastrulation, the cells
of the endoderm lineage slide anteriorly
alongside one another away from the vegetal
pole. These cells move in a fashion similar to
opening a telescope to elongate the gut. Until
now, it was thought that lateral rearrangement
of endodermal cells by convergent extension
was the main contributor to gut elongation.
My project will characterize the telescoping
phenomenon and attempt to distinguish it
from possible convergent-extension
movements that are coincident, or follow the
initial invagination.
The objective of my project is to
analyze the movements of telescoping cells and their molecular control. The sea urchin
is a strong model system for this proposal because of its well-studied endomesoderm
gene regulatory network (GRN) that describes the cell fate specification of the future
larval gut. However, the GRN does not describe specific cell biological events driving
morphogenesis. Still, several molecules known to be involved in aspects of
morphogenesis such as adhesion, signaling, polarity, and cytoskeletal remodeling rely
on the circuitry described in the GRN for their contribution to morphogenesis. Rac1, a
small RhoGTPase, is localized to the adherens junctions prior to gastrulation where it
co-localizes with the adhesion molecule β-catenin . Both cytoskeletal regulators are
removed from adherens junctions of the forming gut. This suggests that the absence of
these molecules at cellular membranes destabilizes adherens junctions of endoderm
cells not only enabling the sliding mechanism of telescoping, but also allowing the
intercalation events of convergent extension while maintaining stability of the forming
larval gut.
Tests of this hypothesis are ongoing. This work and studies connecting the
endomesoderm GRN to gastrulation will provide a framework for characterizing this
remarkable sequence of cell movements in the simplest of deuterstome gastrulation
models.
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Alessandro Mongera/MPI for Developmental Biology, Tuebingen-­‐DE Neural crest long-­term fate mapping in zebrafish: from early ontogeny to adult structures. Neural Crest (NC) is a transient population of multipotent embryonic cells which generates a large number of different tissues that allowed for the evolution of vertebrate-­‐specific features including much of the peripheral nervous system, many craniofacial structures, and integumentary pigment cells, to name a few. Classical studies using the chick-­‐quail chimera approach and more recent analysis in mouse taking advantage of the Cre/LoxP genetic system have defined a NC fate map for embryonic stages. Nevertheless, these studies: 1) have failed to define on a high resolution level the spatial and temporal coordinates of the formation of different lineages because they are still not amenable to non-­‐invasive in vivo imaging; 2) focused mainly on the early development neglecting an accurate description of the adult derivatives. During my Phd I’ve developed in zebrafish a Cre/LoxP system to permanently label NC cells in the early phases of their ontogeny and follow them up to adulthood. By means of confocal in vivo imaging (for embryonic and larval stages) and 2-­‐photon microscopy (for adult fish), my ultimate goal is to link specific NC sub-­‐populations to specific adult structures. The ease access and transparency of the zebrafish embryo enables us to follow in vivo the early branching of the different NC derivatives and to investigate the interaction with other tissues and cell types. In an attempt to define the fundamental steps of NC ontogeny, which could contribute to the formation of different sub-­‐populations and eventually different derivatives, I’m focusing on its early interaction with motor axons: by means of physical ablation and genetic perturbation, my goal is to demonstrate that the metamerized motor axons exiting the spinal cord represent a fundamental cue for the metamerization and the proper formation of the peripheral nervous system. Moreover, I’m building a fine-­‐grained map of the NC derivatives in the adult fish: taking advantage of an inducible version of the Cre/LoxP system, I was able to confirm many ‘classical’ NC derivatives and to define a list of structures which have not been shown to be neural crest derived. !"#$%&'!())*++",'
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!Broadly, I am interested cell invasion across basement
membrane, an event that occurs frequently during normal
development and in diseases such as metastatic cancer. As a
member of Dave Sherwood’s lab, I study this process using
anchor cell invasion, an event during C. elegans vulval
development. My project is focused on basement membrane
dynamics during anchor cell invasion and I am currently
pursuing two areas of research that examine the contribution of
the basement membrane to regulating cell invasion.
The uterine and vulval tissues of the C. elegans hermaphrodite
are separated by two tightly juxtaposed basement membranes.
Early in development, these tissues move freely relative to one another until the anchor cell
invades through both tissues’ basement membranes and into the vulval epithelium, initiating
uterine-vulval connection. We have found that the two tissues stop sliding relative to one another
in a highly stereotyped fashion just prior to anchor cell invasion. By physically separating the
uterine and vulval tissues, we have observed that the uterine and vulval basement membranes
become tightly linked specifically under the anchor cell before invasion. As the anchor cell
invades, the basement membranes fuse into a continuous sheet at the boundary of the hole in the
basement membrane. This process prevents the relative sliding of the basement membranes,
allowing the anchor cell to extend cellular protrusions through the adherent basement membranes.
I am interested in describing this process and elucidating the molecular mechanism that joins the
two basement membranes.
In addition, I am currently investigating the role of SPARC, a secreted matricellular protein, in
regulating cell invasion. Over expression of SPARC appears to enhance invasion, rescuing
defects caused by deleting the transcription factor FOS-1A, a master regulator of anchor cell
invasion. As SPARC is over expressed in many metastatic cancers, I expect it has a conserved
role in promoting cell invasion.
!
Nathaniel Peters – Graduate student, University of Washington
Identifying Tramtrack69 Targets Required for Drosophila Dorsal Appendage Morphogenesis
Tubes are vital for proper organ/tissue function in metazoans and exhibit a myriad of forms and
functions, yet the fundamental molecular mechanisms of tube formation appear to be well
conserved. Elucidating these mechanisms will aid our understanding of the basic molecular
requirements for tube formation, how different species of organisms tailor conserved tube
formation programs to suit their individual needs, and how tube formation defects occur during
development, such as spina bifida. To study tube formation in a genetically tractable system, the
Berg Lab has chosen to study the process of Dorsal Appendage (DA) tube morphogenesis during
Drosophila oogenesis. During the late stages of Drosophila oogenesis, subsets of follicular
epithelial cells that surround each developing oocyte undergo morphogenesis to form DA tubes;
these tubes serve as cellular molds for eggshell respiratory structures present on mature eggs.
DA tube formation provides an appealing model for studying epithelial tube formation because it
occurs in the absence of cell division and apoptosis, permitting us to focus specifically on the
role of coordinated cell movement and shape change in this process.
Tramtrack69 (TTK69) is an essential transcription factor during development; the twin
peaks mutation is a hypomorphic ttk69 allele that specifically affects TTK69 production during
DA tubulogenesis. TTK69 loss in DA-forming follicle cells causes improper regulation of cell
dimensions and migration, and the eventual formation of severely shortened DA tubes. I have
compared gene expression profiles in wild type and twin peaks via microarray to identify targets
and downstream effectors of TTK69 during DA tubulogenesis. I am using in situ hybridization
to confirm candidate gene expression results from my arrays and, to establish functional links
between TTK69 and my array candidates, I am using RNAi and over-expression constructs
driven by follicle cell-specific GAL4 drivers and screening for DA defects. Knockdown of
mirror (one of my microarray candidates) results in notable DA morphology defects, and I am
busy characterizing this result to determine whether mirror interacts with tramtrack.
Additionally, the expression of paxillin, a gene coding for a focal adhesion scaffold protein, is
restricted to the DA-forming follicle cells during DA tubulogenesis and is depleted in twin peaks.
Currently I am completing my RNAi functional analysis of candidate genes and further
characterizing promising candidates through genetic and cytological analysis.
Juliette Petersen (and 6 week old puppy!)
Research Statement: Exploring gene-environment interactions: folic acid and neural tube
closure in Ift88 mice
Neural tube defects (NTDs) are the second most common birth defect1. A seminal study
in 1991 showed that folic acid (FA) supplementation reduced the risk of NTDs by up to 72%2,
and in 1998 the US mandated fortification of the grain supply with FA to help decrease the
incidence of NTD. Since FA fortification, NTD incidence has decreased, however the
mechanism by which FA impacts NTDs has yet to be elucidated. Over 200 genes, when
mutated, lead to NTDs in mice3. Of these, less than 20 have been studied for responsiveness to
FA supplementation, with only 7 mutant lines showing protective effects from increased FA3.
Surprisingly, our lab has shown that a cilia mutant, L3P, has an increased incidence of NTDs
when mice are exposed to a long-term (chronic) folate supplemented diet4. Based on this, my
hypothesis is that certain types of mutations, specifically those that disrupt cilia function,
respond poorly to FA. My goal is to study two alleles that disrupt the Ift88 gene (Ift88null and
Ift88flexo, a hypomorphic allele) which encodes a protein required for cilia formation and Sonic
Hedgehog (Shh) signaling5. These mutant mice exhibit NTD along with disrupted Shh
patterning5. My preliminary data suggests that, as in the case of L3P, FA supplementation
increases the incidence of NTDs in Ift88null mice. I propose to fully study the effect of dietary FA
levels on the Ift88 mouse mutants to explore the mechanisms by which FA negatively affects
neural tube closure, and thus gain insight into how and when FA provides a protective effect
against NTDs.
1. Copp, A.J. & Greene, N.D. Genetics and development of neural tube defects. Journal of
Pathology 220, 217-230 (2010).
2. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study.
MRC Vitamin Study Research Group. Lancet 338, 131-7 (1991).
3. Harris, M.J. Insights into prevention of human neural tube defects by folic acid arising from
consideration of mouse mutants. Birth Defects Res A Clin Mol Teratol 85, 331-9 (2009).
4. Marean, A. & Niswander, L. (unpublished).
5. Huangfu, D. et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins.
Nature 426, 83-7 (2003).
Juliana Roscito
Research Statement
During my PhD thesis, I studied the morphological evolution of body forms in lizards
in a developmental perspective, analyzing the embryological changes involved in the
transition from a lizardlike body form (well-developed limbs and non-elongated body)
to a snakelike burrowing body form (reduced/absent limbs and elongated body). My
future research interests involves a comparative approach to the genetic and
molecular mechanisms of development that led to limb reduction and body
elongation in the several lineages of burrowing reptiles that have evolved whithin
Squamata.
Kuba Sedzinski During my PhD, I have been studying the function of the acto-­‐myosin cortex during cytokinesis, focusing on how forces generated at the poles of the cell are controlled and how they influence cytokinesis mechanics. To address this question I used an interdisciplinary approach by combining molecular cell biology with biophysics. Cytokinesis, as the final step of the cell cycle, has to be tightly regulated in order to ensure successful cell division. Any kind of cytokinesis failure may lead to abnormalities and potentially pathology. In fact, there is a relation between cytokinesis abnormalities and cancer. Cytokinesis requires global control of the mechanical properties of the cell periphery. Although most studies of cytokinetic mechanics focus on the ingression of the contractile ring at the cell equator, an acto-­‐myosin cortex is also present at the poles throughout cytokinesis. Polar contractility calls into question the stability of cytokinesis. Indeed, if contractility is not exactly balanced between the two poles, shape instabilities are likely to arise, where one future daughter cell contracts, propelling cytoplasmic material into the other. Such asymmetric contractions would break the symmetry of the dividing cell and destabilize the position of the cleavage furrow. By quantifying cytoplasmic movements in control dividing cells, we first demonstrated that such shape instabilities are indeed present during cytokinesis. We then showed, both experimentally and theoretically, that a local imbalance in contractile forces or a global increase in polar tension enhance shape instabilities. Finally, we presented strong experimental evidence for a mechanism where the controlled formation of membrane blebs, which is commonly observed at the poles of dividing cells, relaxes cortical tension, thus preventing the build-­‐up of shape instabilities. In summary, we proposed that blebs stabilize the shape of the cleaving cell by buffering polar tension and the resulting intracellular pressure and constitute a fundamental mechanism ensuring the reliability of cell division. As a Post-­‐doc, I want to change my research direction from single cell mechanics towards more complex tissue-­‐like mechanics in order to combine both approaches in the future. My name is Valerie Virta and I am a postdoc in Tom
Sargentʼs lab at the National Institute of Child
Health and Development. I am studying the
dynamics of the Mesenchymal to Epithelial
Transition in differentiating cranial neural crest cells
as they form bony elements in the face.
Lingyu Wang
Third-year graduate student from
University of Miami, Florida, U.S.
Advisor: Athula Wikramanayake
Research: Investigating the molecular
determinants for polarity in the sea
urchin egg
Lab page:
http://www.bio.miami.edu/athulalab/Home.html
Most animal cells are polarized and the
polarity is important for the cell and
embryo functions. I’m using nextgeneration sequencing (NGS) and coimmunoprecipitation (Co-IP) techniques
to investigate the molecular determinants
for the sea urchin egg polarity, also
known as animal-vegetal (A-V) axis.
Furthermore, our lab studies the
evolution of A-V axis of metazoan.
Our lab identified a key protein in canonical/non-canonical Wnt signaling pathway,
Dishevelled (Dsh), is highly enriched in the cortex of vegetal pole in the sea urchin egg.
And the Wnt signaling pathway is activated at 16-cell stage to specify the
endomesoderm. So Dsh and Wnt signaling pathway plays crucial roles in the egg and
embryo polarity establishment. Right now I’m using NGS to investigate what RNA
molecules are also enriched in the cortex of vegetal pole and using Co-IP to study what
PROTEINS are interacting with Dsh and regulating the activity of Dsh. Those molecules
may form a complex and are potentially important for egg and embryo polarity
establishment and maintenance.
Finally, we want to apply what we find into another evolutionarily important species,
Nematostella vectensis, which is a sister group of bilaterians. Therefore, we could study
the evolution path of the A-V axis in metazoan.
John Young
Determining the mechanism of Wnt induced neural posteriorization in the Frog Xenopus I’m working on two projects. First, I’m using zinc-finger nucleases (ZFNs) to introduce
targeted mutations in Xenopus as a novel method to study gene function. Using ZFNs, I’ve
optimized expression, delivery and dose of ZFN RNA to induce several mutant noggin alleles in
the soma of injected animals. I then raised these animals and screened their offspring to find
mutant founders. To date, I have generated three mutant lines of Xenopus tropicalis that have
noggin alleles with varying degrees of function. I plan to use the resulting allelic series
presented by these animals to probe the function of noggin in later development. Second, I’m
interested in morphogen gradients in embryos, specifically how the Wnt protein posteriorizes the
neural plate of the Xenopus embryo. I’ve begun answering this question by determining when
posterior neural genes are initially expressed and when Wnt is capable of inducing neural
posteriorization. I used this data to perform an RNA-Seq screen using an inducible TCF in
neural tissue all the direct and indirect neural Wnt targets. Wnt activated neural tissue revealed 262 genes expressed greater than two-­‐fold when compared to anterior neural tissue. in situ hybridization analysis of highly expressed transcription factors and RNA-­‐
binding proteins showed specific posterior neural expression. I am currently validating the
top direct transcriptional target hits. This data will then be used to find wnt responsive
regulatory elements in these genes that are responsible for their expression in time and in space.
Jane Yu Development and Evolution of the Avian Craniofacial Skeleton Schneider Lab, UCSF I have long been interested in theories regarding the evolvability of animals, plants and
microbes. My work now focuses on development and evolution of the vertebrate face, where
avians are my experimental organisms of choice.
Avian species display a remarkable diversity of facial morphologies, from the small,
pointed, insect-catching beak of the common sparrow, to the narrow, long, nectar-drinking beak
of a hummingbird. Using fate-mapping studies, we know that all of the skeletal elements of the
face and beak are derived from neural crest mesenchyme (NCM), a highly migratory and
multipotent cell population that arises from the margins of the neuroepithelium. We also know
from transplant experiments that NCM plays an instructive role in patterning and growth in the
face (i.e., when we transplant quail NCM into a duck host, the chimera forms a quail-like face
and beak). What remains to be understood is how NCM carries out the components of what is
undoubtedly a very complex task – to pattern beaks with great precision for function in
established niches, but also to allow enough plasticity for evolution in the face of hardship or
changes to the natural environment.
Thus, one of the questions I plan to address in my research is what are the
developmental, cellular, and molecular mechanisms underlying evolvability in avian faces? I
have previously been baffled by the break-neck rate of generation of novel beak morphologies
(a recent paper documents significant beak shape changes within 3-5 generations in wild house
finch population); the seemingly explosive adaptive radiation observed in Darwin’s finches; and
in non-avians, the genesis of over 150 dog types in about as many years of selective breeding.
To begin to understand these surprising phenomena, I am now investigating a series of
transcription factors known to be important in craniofacial skeletal formation, their function,
regulation, and evolution, to begin to understand some of the processes that can modulate the
generation of heritable, selectable, phenotypic variation.