New York Area C. elegans Discussion Group Meeting (1)

New York Area C. elegans Discussion Group Meeting

Thursday, December 2, 2010

The New York Academy of Sciences

Presented By

 

The nematode Caenorhabditis elegans has emerged as a powerful model organism in experimental biology. The accessible anatomy and cell biology, facile genetics, and molecular toolkit available to researchers using this animal have led to fundamental broadly-applicable insights into many areas of biology including neurobiology, behavior, evolution, genomics, cell biology, physiology, development, immunity and aging. Three Nobel prizes over the past eight years have recognized C. elegans researchers for their seminal discoveries in the fields of programmed cell death, RNA interference, and live-cell imaging.

The New York area C. elegans Discussion Group brings together members of local area C. elegans laboratories with diverse biological interests twice annually to discuss their recent studies. The group features presentations by senior researchers as well as students, postdocs, and young investigators, often presenting unpublished results. Meetings provide an opportunity to exchange ideas, network, and form research collaborations.

Agenda

*Presentation times are subject to change.


1:00 PM

Understanding the C. elegans wiring diagram, after (almost) 25 years: perspectives, results, and unanswered questions
Cori Bargmann, PhD, The Rockefeller University 

1:45 PM

Convergent Evolution Affecting Candidate Pheromone Receptors in Caenorhabditis
Patrick T. McGrath, PhD, The Rockefeller University

2:10 PM

Complexin has opposite Effects on two modes of Synaptic Vesicle Fusion
Jeremy Dittman, MD, PhD, Weill Cornell Medical College

2:35 PM 

Coffee Break

3:15 PM

Epidermal Growth Factor Signaling Activates the Ubiquitin Proteasome System in Response to Aging in C. elegans
Chris Rongo, PhD, Rutgers University

3:40 PM

Endogenous RNAi and Insulin-like Signaling Work in Parallel to Control Neuronal Development in C. elegans
Lisa Kennedy, Columbia University Medical Center

4:05 PM

Quantitative Genetic Dissection of Thermal Avoidance Behavior in C. elegans
Rajarshi Ghosh, PhD, Princeton University

4:30 PM

Networking Reception

Speakers

Organizers

Jane Hubbard, PhD

Skirball Institute of Biomolecular Medicine

E. Jane Albert Hubbard, PhD, is an Associate Professor in the Department of Pathology and the Skirball Institute Developmental Genetics Program at the New York University School of Medicine, where she has been since 2007. From 1998-2007, she was on the faculty of the NYU Department of Biology. Dr. Hubbard was a Damon Runyon postdoctoral fellow in the laboratory of Dr. Iva Greenwald in the Department of Biochemistry and Molecular Biophysics at Columbia University. In 1993, after work in Dr. Marian Carlson's laboratory, she graduated from Columbia University with a PhD in Genetics and Development. Her laboratory studies germ cell development in the model organism C. elegans with a focus on the control of germline proliferation. She is a Program coordinator for Developmental Genetics and course director for three graduate courses (Foundations in Developmental Genetics (I and II), and Stem Cell Biology).

Cathy Savage-Dunn, PhD

Queens College, CUNY

Cathy Savage-Dunn, PhD, is a Professor in the Department of Biology at Queens College, CUNY. She received her PhD in 1992 from Columbia University working with Dr. Martin Chalfie on the specification of a cell-specific microtubule type. She worked as a postdoctoral fellow with Dr. Iva Greenwald at Princeton University in 1992 and with Dr. Richard Padgett at Rutgers University from 1993-1998. Dr. Savage-Dunn's research interests lie in the areas of signal transduction and development. Her laboratory studies the conserved and multifunctional TGFβ signaling pathway, using a genetic approach in the nematode C. elegans. Dr. Savage-Dunn is a Deputy Executive Officer of the CUNY PhD Program in Biology and has been a co-organizer of New York Area C. elegans meetings since 1998.

Shai Shaham, PhD

The Rockefeller University

Shai Shaham is an Associate Professor at the Rockefeller University in New York. After completing doctoral studies at the Massachusetts Institute of Technology with H. Robert Horvitz, and postdoctoral studies at the University of California, San Francisco with Ira Herskowitz and Cori Bargmann, Shaham joined Rockefeller as an Assistant Professor in 2001. Since then, his lab has continued studies of programmed cell death, initiated during his graduate studies, uncovering a novel morphologically conserved pathway for cellular demise. His lab has also developed the model organism C. elegans as a unique setting to study glial cells, the major components of vertebrate nervous systems. These studies have revealed that glia play essential and dynamic roles in the development and function of the nervous system.

Jennifer Henry, PhD

The New York Academy of Sciences


Keynote Speakers

Cori Bargmann, PhD

The Rockefeller University

Cori Bargmann is the Torsten N. Wiesel Professor and associate director of the Shelby White and Leon Levy Center for Mind, Brain and Behavior at Rockefeller University, and an investigator at the Howard Hughes Medical Institute.  Her lab studies the neuronal and genetic regulation of behavior in the nematode C. elegans.  Genes, the environment, and experience interact to shape an animal's behavior.  C. elegans has only 302 neurons, but shows remarkable sophistication in its behaviors, making it an ideal subject in which to study these interactions. The laboratory investigates how neural circuits develop, identifies genes and neural pathways for circuit function, and asks how sensory inputs and internal states regulate circuits.


Speakers

Jeremy Dittman, MD, PhD

Weill Cornell Medical College

Jeremy Dittman joined the faculty at Weill Cornell Medical College as an Assistant Professor of Biochemistry in 2008. Jeremy received a BS in Biochemistry at Stanford University in 1992 where he learned neurophysiology in the laboratory of Richard Aldrich. Jeremy received MD and PhD degrees from Harvard Medical School in 2000. His thesis work was carried out in the laboratory of Wade Regehr and focused on the neurobiology of synaptic transmission and the role of presynaptic calcium. In pursuit of a more detailed molecular picture of the events underlie neurotransmission, Jeremy joined Josh Kaplan's lab and switched from rodent brains to worms. During his postdoc, Jeremy combined quantitative imaging with molecular genetics in C. elegans as a model system for studying synaptic transmission. Current work in the Dittman lab explores the molecular mechanisms that underlie synaptic vesicle fusion and endocytosis. In particular, the lab has focused on complexin, a molecule thought to play a crucial role in the fusion process. The lab is also interested in developing techniques for imaging the dynamics of synaptic proteins in living synapses.

Rajarshi Ghosh, PhD

Princeton University

I completed my Bachelor's degree from University of Calcutta in Chemistry major and my Masters from the same university in Biochemistry.

I earned my Ph.D. under the supervision of Dr. Scott Emmons from Albert Einstein College of Medicine in 2007 where I studied the neurogenetics of C.elegans behavior. I am currently conducting postdoctoral research in Dr. Leonid Kruglyak's laboratory at Princeton University. My post-doctoral research is aimed at understanding the genetic architecture and the causative genetic polymorphism(s) that allow heritable differences in sub-steps of a behavioral output using a quantitative genetics approach in the nematode C. elegans.

Lisa Kennedy

Columbia University Medical Center

Lisa Kennedy received her B.S. in Biological Sciences from Cornell University in 2005. She then went on to work as a Technician in the laboratory of Dr. Ronald Crystal at Weill Cornell Medical College for two years prior to entering graduate school in 2007. Lisa is currently a fourth year student in Alla Grishok's lab at Columbia University Medical Center.

Patrick McGrath, PhD

The Rockefeller University

Patrick McGrath is currently a postdoctoral researcher in Cori Bargmann's laboratory exploring the genetic basis of behavioral trait variation between individual strains of C. elegans. Patrick received a BS in Astronomy from the University of Illinois in Urbana/Champaign. He received his PhD in Physics from Stanford University for his work on understanding the genetic circuitry controlling a bacterial cell cycle.

Chris Rongo, PhD

Rutgers University

My primary research interest is in understanding subcellular localization and cell trafficking mechanisms using a combination of genetic, cell biological, and molecular approaches. I became interested in subcellular localization as a graduate student with Dr. Ruth Lehmann at MIT, where I studied the process of mRNA localization and translational regulation using genetic and biochemical approaches in Drosophila. As a postdoctoral fellow with Dr. Josh Kaplan (at MGH, then UC Berkeley), I began using C. elegans to study glutamate receptor trafficking to synapses in vivo. As an Assistant Professor at Rutgers, I expanded my research to screen for novel regulators of glutamate receptor localization and became interested in the function of the Ubiquitin Proteasome System in multicellular organisms. I am currently an Associate Professor at Rutgers, and my lab continues to study the basic mechanisms of membrane trafficking in both neurons and non-neuronal cells using genetics, cell biology, biochemistry, and behavioral analysis. In addition, we are beginning to examine how neurons use these mechanisms to respond to oxidative stress, hypoxia, and aging.


Sponsors

For sponsorship opportunities please contact Cristine Barreto at cbarreto@nyas.org or 212.298.8652.

Academy Friend

    Abstracts

    Understanding the C. elegans wiring diagram, after (almost) 25 years: perspectives, results, and unanswered questions

    Cori Bargmann, PhD, The Rockefeller University

    Abstract not supplied

    Complexin has opposite effects on two modes of synaptic vesicle fusion

    Jeremy Dittman, MD, PhD, Weill Cornell Medical College

    Synaptic transmission can occur in a binary or graded fashion depending on whether transmitter release is triggered by action potentials or by gradual changes in membrane potential. Molecular differences of these two types of fusion events and their differential regulation in a physiological context have yet to be addressed. Complexin is a conserved SNARE-binding protein that has been proposed to regulate both spontaneous and stimulus-evoked synaptic vesicle (SV) fusion. Here, we examine complexin function at a graded synapse in C. elegans. Null complexin (cpx-1) mutants are viable although nervous system function is significantly impaired. Loss of CPX-1 results in a 3-fold increase in the rate of tonic synaptic transmission at the neuromuscular junction while stimulus-evoked SV fusion is decreased 10-fold. A truncated CPX-1 missing its C-terminal domain can rescue stimulus-evoked synaptic vesicle exocytosis but fails to suppress tonic activity, demonstrating that these two modes of exocytosis can be distinguished at the molecular level. A SNARE-binding CPX-1 variant also rescues evoked but not tonic neurotransmitter release. Finally, tonic but not evoked release can be rescued in a syntaxin point mutant by removing CPX-1. Rescue of either form of exocytosis partially restores locomotory behavior indicating that both types of synaptic transmission are relevant. These observations suggest a dual role for CPX-1: suppressing SV exocytosis driven by low levels of endogenous neural activity while promoting synchronous fusion of SVs driven by a depolarizing stimulus. Thus, patterns of synaptic activity regulate complexin’s inhibitory and permissive roles at a graded synapse.

    Quantitative genetic dissection of thermal avoidance behavior in C. elegans

    Rajarshi Ghosh, PhD, Princeton University

    Individuals within and between species often exhibit heritable variation in sub-steps of a behavioral sequence. What genetic changes and architecture allow for such plasticity? Does the genetic change alter the connectivity of neural circuitry or logic of a neural circuit operation or both? To address these questions we transiently raised the local temperature around a worm by an IR laser and recorded several aspects of the resulting escape response. Typically upon sensation of a thermal impulse worms exhibit a behavioral sequence in which they enter a pause state followed by reversals and an omega turn and resumption of forward movement. We quantitatively characterized several aspects of this sensori-motor transformation during escape response for the laboratory strain (N2) and a wild isolate (CB4856) of C. elegans for stimuli resulting in 0.3, 0.8, 3 or 7.5ºC rise in temperature. We found that various aspects of response to 0.3ºC increases in temperature exhibited the greatest difference between these two strains. In order to examine the nature and extent of pleiotropy we measured several traits including but not limited to speeds at every 180 milliseconds during the assay, probability of worms switching between various states, duration and number of reversals, probability of a reversal ending in omega turn in recombinant inbred lines made from N2 and CB4856 parent strains. We identified several quantitative trait loci (QTL) underlying different attributes of escape response. For example, the reversal duration and the number of sinusoidal waves during reversals are modulated by one common locus on Chromosome V as well as distinct QTL on Chromosomes IV and X respectively, and the probability of switching to omega turns is regulated by additive QTL on Chromosomes IV and III. Thus the behavioral states resulting from thermal impulse and switching between them are genetically separable. We will discuss the progress made in mapping genes underlying the QTL.

    Endogenous RNAi and Insulin-like signaling work in parallel to control neuronal development in C. elegans

    Lisa Kennedy, Columbia University Medical Center

    We are investigating the biological roles of endogenous RNA interference in Caenorhabditis elegans. Specifically, we have identified migration and axon guidance defects in the hermaphordite-specific neurons (HSNs) in a subset of RNAi pathway mutants. These mutants include the following: an RNAi-promoting chromatin factor, Zinc Finger Protein 1 (ZFP-1); a dsRNA-binding protein of the Dicer complex, RDE-4; a dicer-related helicase (DRH-3) and a nuclear Argonaute, CSR-1, which is chromosome-segregation and RNAi deficient.

    Furthermore, we have observed phenotypic similarities between a conserved FOXO family transcription factor, DAF-16, a major transcriptional output repressed by insulin-like signaling and ZFP-1. Among these shared phenotypes are HSN under-migration and axon guidance defects. A daf-16; zfp-1 double mutant exhibits enhanced defects in both axon guidance and HSN under-migration, suggesting that daf-16 and zfp-1 work in parallel genetic pathways to regulate HSN development. Additionally, we have determined that constitutively expressing DAF-16 in the nucleus by removing age-1 activity leads to overmigration of the HSN in a DAF-16 dependent manner, thereby further implicating insulin-like signaling as an important modulator of cell migration in C. elegans.

    We are currently investigating candidate targets of both endogenous RNAi components and DAF-16 that may regulate neuronal genes required for proper migration and axon guidance.

    Convergent evolution affecting candidate pheromone receptors in Caenorhabditis

    Patrick McGrath, PhD, The Rockefeller University

    We are using C. elegans as a model for understanding how genetic variation controls phenotypic variation between individuals of a species. In response to high population density and other cues, C. elegans larvae enter the alternative dauer diapause development pathway. Local population density is assessed by animals releasing and sensing a set of closely related pheromones known as ascarosides. We have found that three Caenorhabiditis strains that were grown in liquid culture for long periods have become resistant to dauer pheromones, suggesting that dauer resistance has been positively selected for in these conditions. We mapped the defect in one of these strain and found that it is affected by multiple loci. Part of the defect maps to a deletion of two ASI-expressed chemosensory receptors. Animals lacking these receptors are specifically defective in forming dauers in response to the ascaroside C3, suggesting that they could be C3 pheromone receptors. Independent deletions in these receptors have been identified in each of the three strains that were grown in liquid (two C. elegans strains and one C. briggsae strain), suggesting that adaptation to liquid growth targets the same genes even in species that have been separated for millions of years.

    Epidermal Growth Factor Signaling Activates The Ubiquitin Proteasome System In Response To Aging In C. elegans

    Chris Rongo, PhD, Rutgers University

    Epidermal growth factor (EGF) signaling regulates cell growth, proliferation, and differentiation, and has recently been implicated in regulating lifespan, although the mechanism remains unclear. Here we examine the function of EGF signaling in lifespan in adult C. elegans. We find that EGF signaling regulates lifespan via the Ras-MAPK pathway and the PLZF transcription factors EOR-1 and EOR-2. Using microarray analysis, we found that EGF signaling regulates the expression in adults of genes involved in lipid metabolism, oxidative stress, heat shock response, and the ubiquitin/proteasome system (UPS). We employed GFP-based reporters of both global UPS activity and oxidative stress to test whether EGF signaling alters protein homeostasis, a critical facet in aging and cellular degeneration. We find that EGF signaling triggers an increase in UPS activity and in the levels of polyubiquitinated proteins in epithelial cells as animals mature into adulthood. Through a forward genetic approach, we identified 41 components of the UPS machinery required for this increase in UPS activity, including CHN-1, HECD-1, and UFD-2 (E3/E4 ligases comprising the UFD complex); CUL-1and SKR-5 (F-box E3 ligases); and several ubiquitin-like molecules. Animals that fail to upregulate UPS activity via EGF signaling and the UFD complex have reduced lifespans and indications of oxidative stress. Taken together, our results suggest that EGF signaling and the UFD complex maintain protein homeostasis by augmenting UPS activity as animals mature into adulthood.

    *Additional abstracts coming soon.

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