Graduate Summer Colloquium 2006: Abstracts

Allison Weber

“Association Mapping in Teosinte: How Natural Allelic Variation Controls Phenotypic Variation”

Understanding the inheritance of complex traits is a fundamental goal of quantitative genetics.

Lisa Johns

“Interactions between SMG proteins and target mRNAs during C. elegans NMD”

Messenger RNAs that contain premature termination codons are selectively degraded in eukaryotes, a phenomenon termed "nonsense-mediated mRNA decay" (NMD).

Jasmine Parvaz

“Analysis of Nonstop mRNA Decay in Caenorhabditis elegans”

Nonstop decay (NSD) is an mRNA degradation pathway identified in yeast

Min Ni

“A novel regulator of development: VosA is necessary for spore maturation and proper down-regulation of brlA in Aspergillus nidulans”

Asexual sporulation (conidiation) is a common reproductive mode for many fungal species. In Aspergillus nidulans conidiation requires activities of multiple developmental activators. However, our recent studies showed that a crucial step for initiation of conidiation is removal of repressive effects imposed by multiple negative regulators.

Zhen Zhang

“The microRNA-Processing Enzyme Dicer is Essential for Somite Cell Survival”

Dicer is an RNAseIII enzyme essential for microRNA (miRNA) maturation. The mature miRNAs act in a sequence-dependent manner in repressing gene expression either on the transcript or protein level. MiRNAs have been shown to function in multiple developmental processes, including brain and heart development. I am interested in investigating miRNA function in somite formation. Somites are transient mesodermal blocks along the anterior-posterior axis of vertebrate embryos. They give rise to vertebra, skeletal muscle and dermis in the adult. The generation of somites is a process controlled by oscillators and gradients in the presomitic mesoderm (PSM). Thus somite formation is exceptionally sensitive to the expression level of critical genes. In this study, we conditionally inactivated Dicer in the mesoderm cells to examine the collective effect of miRNAs on somitogenesis in mice. The mutant embryos exhibit apparent small body size and short tail at Embryonic Day (E) 11.5, and die shortly after. More detailed analyses show that Dicer is essential for somite cell survival but is dispensable for somite initiation and somite differentiation. The possible implication of this finding will be discussed.

Emily Putiri

“mission impossible, a zebrafish maternal effect mutation that affects endoderm specification and gastrulation”

In early animal development, the basic body plan is established during gastrulation: the primary axes are determined and the three embryonic germ layers, the ectoderm, mesoderm, and endoderm, are formed. These events require a complex coordination of correct cell fate specification and morphogenetic cell movements. Analyses of mutants that affect these events provide a framework for understanding the molecular controls of gastrulation.

mission impossible (mis) is a zebrafish maternal effect mutation that disrupts the specification of endodermal precursors during gastrulation. The mutation also disrupts morphogenetic cell movements, resulting in embryo lysis during late gastrulation. Epistasis analysis indicates that mis functions at the level of or downstream of the gene casanova, which encodes a transcription factor within the endoderm specification pathway. Segregation analysis has identified a 1.3 cM region in chromosome 15 that contains the affected gene, and we are currently narrowing this region through fine mapping analysis. I will present progress on the phenotypic characterization and molecular identification of mis.

Carolyn Neal

“Exploring the early events of root gravity and touch signal transduction with a proteomics approach”

The Masson lab conducted a proteomics screen of Arabidopsis root caps to identify proteins whose abundance and/or modification change early in response to gravity stimulation. The study identified proteins with interesting temporal patterns of response to gravity and touch stimulation, and groups of differentially regulated proteins with clearly related functions that had not previously been implicated in gravity or touch signaling. I recently initiated a project aimed at identifying and characterizing plants with mutations in some of these differentially controlled proteins in hopes of better understanding early events in gravity signal transduction.

Laura Vaughn

“Quantitative trait analysis of Arabidopsis thaliana root behavior on a tilted hard agar surface”

Arabidopsis thaliana roots grown on hard, tilted agar surfaces show characteristic behaviors. Two such behaviors are root growth away from the vertical, known as skewing, and alternating tip growth from right to left resulting in a wave-like pattern. These phenotypes are complex and vary somewhat between the roots of an individual Arabidopsis accession. They also differ greatly when multiple accessions are compared. To discern genetic and environmental components of these traits, quantitative trait loci (QTL) mapping and analysis has been undertaken. The goal of the study is to elucidate some of the genes contributing to the behaviors and their ecological and evolutionary significance.

Kelley Harris

“Dicer Function is Essential for Lung Epithelium Morphogenesis ”

Dicer is a cytoplasmic, ribonuclease III enzyme that processes microRNAs (miRNAs) and small inhibitory RNAs (siRNAs) to their mature forms. In general, mature miRNAs bind with imperfect complementarity within the 3′UTR of their target genes to illicit translational repression. Conversely, mature siRNAs form perfect duplexes with their targets and direct cleavage of the target mRNAs. In mouse, a null allele of Dicer exhibits an embryonic lethal phenotype prior to gastrulation. Here we bypass this early lethality and investigate the role of DICER in lung formation using a conditional knockout approach.

Lung branching morphogenesis is a major event during lung development that produces the characteristic arborization of the respiratory tree. We found that inactivating Dicer specifically in lung epithelium leads to an arrest of the branching process. We will present data toward understanding the cellular and molecular mechanism of Dicer function in lung formation.

This research is significant for a number of reasons. Firstly, a basic understanding of mammalian lung development is at the foundation for future therapeutic measures aimed at treating asthmsa and lung cancer. In addition, this study is novel because our data indicates that DICER may regulate a key branching morphogenesis gene through miRNA regulation.

Sheng Gao

“Characterization of Smad Complexes Bound to Dpp-Responsive Silencer Elements”

Transcriptional regulation by TGF-beta signaling is mediated by the Smad family of transcription factors. Recently it has been shown that a complex of the Drosophila Smad proteins, Mad and Medea, binds with high affinity to silencer elements that repress brinker and bag of marbles in response to Dpp signaling. Here we report that these silencers are bound by a heterotrimer containing two Mad subunits and one Medea subunit. We found that the MH1 domains of all three subunits contributed directly to sequence specific DNA contact, thus accounting for the exceptionally high stability of the Smad silencer complex. The Medea MH1 domain binds to a canonical Smad box (GTCT), while two Mad MH1 domains bind to a GC-rich sequence resembling Mad binding sites. The consensus for this sequence, GRCGNC, differs from that of the canonical Smad box, but we found that Mad binding nonetheless required the same beta-hairpin amino acids that mediate base specific contact with GTCT. Binding was also affected by alanine substitutions in Mad and Med at a subset of basic helix 2 residues, indicating a contribution to binding of the GRCGNC and GTCT sites. We also provide evidence that binding to GRCGNC site is achieved by contact of the two Mad subunits that overlaps across the two central base pairs of the site. This topology is supported by mutational analysis of the binding site. Also consistent with the model is disruption of binding by mutation of Glu39, Glu40 and Arg94 which are predicted to lie at the interface of the two overlapping Mad MH1 domains. Overlapping Mad sites predominate in Dpp response elements, consistent with a high degree of specificity in response to signaling.

Hua Wang

“Genetic dissection of modifiers of ApcMin during the development of mammary tumors”

Breast cancer develops through multiple steps which are rigorously controlled by genetic regulators. With a well characterized mouse model the ApcMin/+mouse, we aimed to identify loci affecting tumor progression and tumor growth. More than 90% of C57BL/6J (B6) ApcMin/+ female mice develop an average of four mammary squamous cell carcinomas by 75 days after ENU treatment while ENU-treated FVBB6 F1 ApcMin/+ female mice develop an average of four alveolar hyperplasias but squamous cell carcinomas (SCC) or adenocarcinomas only rarely and with increased latency. We used standard backcross analysis to search for loci that affect tumor progression and growth in the ApcMin/+ mice. Four novel mammary modifier loci were identified. The QTL on chromosome 9 significantly affects tumor number. The QTL on chromosome 4 suggestively affects tumor number but significantly affect tumor latency. The QTL on chromosome 6 interacts with QTL on chromosome 4 and 9 to affect tumor number. Interestingly, the QTL on chromosome 18 specifically affects tumor latency and shows at least additive interaction with QTL on chromosome 4. To better understand the effect of FVB background on tumor development, we produced FVB- ApcMin/+ congenic mice. A striking phenotype is most tumors are adenocarcinoma in contrast with SCC in B6-ApcMin/+ mice. The molecular mechanisms underlying the different tumor phenotypes are being investigated.

Yujie Wang

“Tip of An iceberg ? Genetic and Molecular study on Drosophila tipA mutant ”

Drosophila mutant tipA (temperature induced paralysis A), is a classic temperature sensitive mutant and has been around for many years. Yet, the gene that?s responsible for the ts paralysis phenotype has not been discovered. Through a combination of genetic and molecular approaches, we are able to map the ts paralysis phenotype to the gene Eps15.

Eps15, which stands for EGFR Pathway Substrate 15, was originally discovered in mammalian cell culture, as a substrate for the EGFR tyrosine kinase. It?s been shown in other organisms that Eps15 is involved in clathrin mediated endocytosis. Here, we found the drosophila Eps15 can genetically interact with Dynamin and other components in the endocytic pathway, confirming its role in endocytosis; further more, it also shows genetic interaction with nervous wreck, an adaptor protein which regulates actin cytoskeleton organization at drosophila neuromuscular junction. A model has been proposed that Eps15 functions as an adaptor protein between endocytosis and actin re-organization, and more experiments have been proposed to address this hypothesis.

John Stanga

“Using Forward Genetics to Identify Novel Participants of Root Gravitropism Signal Transduction”

Arabidopsis roots perceive gravity and reorient their growth accordingly. The root cap is necessary for a full response to gravity. Starch-dense amyloplasts within the columella cells of the root cap are important for gravitropism, as starchless mutants (pgm1) display an attenuated response to gravistimulation. However, our understanding of the molecular events controlling this behavior is incomplete. The altered response to gravity 1 (arg1) mutant is known to be involved with the early phases of gravity signal transduction. arg1 responds slowly to gravistimulation, and is in a genetically distinct pathway from pgm1. arg1 seeds were mutagenized with EMS to identify new mutants that would enhance the gravitropic defect of arg1 and therefore be members of a separate genetic pathway. The roots of two such mutants, mar1 and mar2, grow in random directions only when arg1 is present. Both mutants possess mutations in genes encoding members of the Translocon of the Outer Membrane of Chloroplasts (TOC) complex. Their exact contribution to the determination of root growth direction remains the subject of ongoing endeavors.

Lan Yi

“MEIS1: a transcription factor essential for mouse lung lobe separation”

Lung is an extremely important organ for air exchange in terricolous vertebrates. It is usually constituted with several lobes on both side of the trachea. Within species, the number and shape of the lobe is always defined, suggesting it is under control of a very stereotypical mechanism during the development. However, to date, very little is known about how this mechanism works. In our study, we are trying to explore this mysterious field by using mouse as a model organism. In mouse lung, there are four lobes on the right side and one lobe on the left side. We found that a Tale domain transcription factor Meis1 is expressed in the developing mouse lung mesoderm since embryonic day 11.0, the stage when the four right lobes start to form. In the homozygous Meis1 knock out mice, all the four right lobes can not be probably separated. We examined key gene expressions in the mutant mice and compared to other existing mutations that carry the similar lobation defects. We then hypothesize that extra cellular matrix proteins in the mesenchyme are required for lung lobe to separate and form the regular shape and transcription factor Meis1 might be a very important upstream mediator for these set of proteins in the lung and possibly in other organs.

Andy Klocko

“Identification of components of σ⁷⁰ important for the interaction between Eσ⁷⁰ and 6S RNA”

The E. coli 6S RNA is a 184 nucleotide untranslated RNA that plays a role in cell survival under nutrient-limiting conditions. 6S RNA forms a phylogenetically conserved secondary structure featuring a single-stranded bulge centralized in a mostly double-stranded structure. 6S RNA deficient cells (ssrS1) exhibit changes in viability under several defined growth conditions, suggesting 6S RNA is involved in a number of cellular processes.

6S RNA regulates transcription by binding RNA polymerase (RNAP) holoenzyme containing the σ⁷⁰ subunit (Eσ⁷⁰). σ⁷⁰ conveys specificity to RNAP, and much is known about the conserved domains of σ⁷⁰ and the contacts with promoter DNA. This information can be used to help understand how 6S RNA binds to Eσ⁷⁰. Current data suggests that 6S RNA might mimic promoter DNA and possibly bind to the same domains of σ⁷⁰ that bind promoter DNA.

Detailed understanding of the manner in which 6S RNA binds RNAP, as well as the 6S RNA-based mechanism of regulation of transcription, await further experimentation. To date, several procedures have suggested one of the conserved, DNA-binding domains of σ⁷⁰ may be important for the interaction between Eσ⁷⁰ and 6S RNA. However, more work needs to be done to completely understand 6S RNA binding to Eσ⁷⁰.

Adeline veillet

“Fine-mapping and characterizing the mammary susceptibility locus Mcs5c”

In order to understand the genetic basis of breast cancer, we are making use of rat strains that differ in their susceptibilities to carcinogen-induced mammary tumors. A quantitative trait loci (QTL) analysis was done using the Wistar-Furth susceptible strain (average tumor number of 8) and the Wistar-Kyoto resistant strain (average tumor number < 1). The F1 were backcrossed to the WF susceptible strain and the progeny was phenotyped and genotyped at markers throughout the genome. This analysis led to the discovery of 4 loci that are linked to tumor incidence as well as a modifier locus.

Mcs5, the QTL with the strongest LOD score was further characterized using congenic lines. Mapping analysis of Mcs5 led to the discovery of at least 3 loci (Mcs5a, b and c) that affect tumor numbers. The Wistar-Kyoto allele of two of these loci reduces while the third increases tumor number, compared with WF controls.

The present study focuses on Mcs5c, which reduces tumor number by 50-60%. We are currently working on narrowing the interval using congenic lines, as well as characterizing some of the biological features of that locus.

Katie Clark

“A High-Throughput Approach to Analyze the Functions of the MAPK Gene Family in Arabidopsis”

One goal of the Krysan lab is to analyze the functions of the Mitogen-Activated Protein Kinase (MAPK) gene family in Arabidopsis. MAPKs are involved in a variety of signaling pathways in eukaryotes. For the majority of the 20 MAPK genes in Arabidopis plants with a mutation in a single MAPK gene are not distinguishable from wildtype. The next step is to create plants with combinations of mutations. It is impossible to predict which of the thousands of combinations will yield an interesting phenotype. I am creating plants that are heterozygous for all 20 mutations and let the plant do the work. The offspring of these 20-tuple plants will segregate for all possible combinations of mutations. We will examine the offspring for interesting phenotypes and determine their genotype. With this approach, we will determine which MAPK genes are involved in specific signaling pathways.

Britt Johnson

“The Role of Rs1h in Retinal Cell Adhesion and Maintenance of Synaptic Structure and Function”

X-Linked Retinoschisis (XLRS) is a common form of inherited macular degeneration caused by mutations in the RS1 gene. Affected juvenile males have a loss in retinal function and schisis (splitting) of the retina. Although RS1 is thought to play a role in cell adhesion, the exact molecular function of RS1 remains elusive. A splice site mutation in the murine homologue of RS1, Rs1h, causes phenotypes similar to XLRS males. Rs1h mutant mice have a reduced ERG b-wave, which suggests a loss in neurotransmission. Consistent with this ERG pattern, we observed morphological abnormalities of the synapses such as ectopic presynaptic terminals and abnormal extension of neurites, in addition to retinal schisis in these mice. These results demonstrate that RS1H has functional significance in the morphology and function of the synapse as well as in retinal cell adhesion.

The main focus of our study is to understand the molecular function of Rs1h through identification of its genetic and physical interacting factors. We have identified a single major modifier locus, which rescues the schisis phenotype in Rs1h mutant mice. We also found that mice carrying a mutation in a potential RS1H binding protein, collagen II alpha 1 subunit (Col2α1) show similar phenotypes to Rs1h mutant mice. Understanding these interactions may provide insight as to how Rs1h plays a role in synaptic maintenance and cell adhesion.

Christopher Mayne

“Dissection of BAFF-R Function in B Lymphocyte Survival and Autoimmunity in BAFF-R Mutant Mice”

Lupus, an autoimmune disease of unknown etiology, affects greater than five million individuals worldwide. This systemic disease is thought to reflect autoantibody-mediated damage due to a failure of B lymphocyte tolerance. Excessive amounts of the cytokine BAFF were observed in humans and mice with lupus. Since BAFF utilizes the receptor BAFF-R to signal survival and maturation in peripheral B lymphocytes, it is currently thought that excessive BAFF-R signaling predisposes individuals to lupus. Conversely, we have discovered a lupus-like condition in A/WySnJ mice harboring a spontaneous BAFF-R mutation that disrupts BAFF-R signaling. Importantly, we genetically linked this mutation to the lupus phenotype, providing the first evidence relating disrupted BAFF-R signaling to a lupus-like condition. Currently, the signaling mechanism of BAFF-R and its A/WySnJ mutant form remain largely unknown. We hypothesize that the BAFF-R signaling defect causes a break in B lymphocyte tolerance. Our recent research utilizes retroviral transduction to define regions of BAFF-R involved in survival and maturation signaling in vivo. Additionally, we are constructing congenic strains to evaluate whether the A/WySnJ form of BAFF-R is necessary and sufficient to break B cell tolerance. This research will shed light on BAFF-R signaling mechanisms, while establishing defective BAFF-R signaling as a novel genetic basis for autoimmunity.

Robert Schmitz

“VIN5 is a Histone Arginine Methyltransferase that is Required for Vernalization-Induced Epigenetic Silencing of FLC in Arabidopsis”

Winter-annual varieties of Arabidopsis require an exposure to the prolonged periods of cold experienced during the winter to flower rapidly in the following spring. This process is known as vernalization. Vernalization acts to silence the strong floral repressor FLC (FLOWERING LOCUS C) via formation of a heterochromatin-like structure that is stably maintained throughout cell divisions. A forward genetic screen for mutants that fail to flower rapidly after vernalization treatment was performed to determine the molecular nature of this epigenetic phenomenon. One of these mutants, vernalization insensitive 5, contains a mutation in a protein arginine methyltransferase. This class of proteins can methylate arginine residues on histone tails that contribute to repression of gene activity and ultimately heterochromatin formation. In vin5 mutants, FLC is not stably repressed and as a result flowers late after vernalization treatment. While FLC is the major target of the vernalization pathway it is also under constant repression by the autonomous pathway (although the repressive activities of this pathway are not potent enough to cause early flowering in winter annuals). Mutations in components of the autonomous pathway result in late-flowering phenotypes in summer-annuals (early-flowering non-vernalization requiring genetic backgrounds) and enhance the late-flowering phenotypes observed in winter annuals. Introgression of the vin5 mutation into a summer-annual background revealed a late-flowering phenotype. Thus, the actions of VIN5 are required for both the autonomous pathway and the vernalization pathway to repress FLC. Although vernalization could not cause rapid flowering of vin5 in a winter-annual it could rescue the late-flowering phenotype of vin5 observed in the summer annual. Therefore, arginine histone modifications provided by VIN5 and commonly associated with heterochromatin are not an absolute requirement for gene repression, but instead are enhancers of the silenced state.

Xiaoyan Ge

Bharti Solanki

“Role of aura in cytokinesis and germ plasm segregation”

A fundamental biological phenomenon in animal cells is the process of cell division, an event that divides daughter cells in two. The completion of cytokinesis often results in the asymmetric segregation of cell determinants, thereby allowing the two daughter cells to proceed towards diverse cell fates. Many of these processes are driven and regulated by maternal products already present in the unfertilized egg. A recessive maternal-effect mutation, aura, was identified in a zebrafish screen for maternal-effect mutations. Preliminary evidence indicates that aura affects several events during early development that may be dependent on actin cytoskeletal rearrangements and/or membrane dynamics. aura mutants exhibit defects in cortical granule exocytosis, β-catenin aggregation and segregation, late cytokinesis and vasa RNA recruitment to the furrow. A positional cloning approach is being used to determine the location and identity of aura. Cell biology, genetic, and experimental approaches are being used to characterize aura gene function. Together these studies will contribute to understanding the function and regulation of aura during the processes of cytokinesis and germ plasm segregation.

Zachary Larson-Rabin

Nicholas Shera

“Cancer genomics: discovery and characterization of structural alterations in oligodendroglioma via single molecule analysis”

A comprehensive understanding of how human genetic diversity translates to phenotypic distinction requires genomic analysis dealing with emergent alterations indiscernible by single nucleotide polymorphic markers. New evidence has revealed that sub-microscopic alterations, termed structural alterations, encompassing genomic regions 1 kb - 900 kb in size are significant factors in human disease and diversity. As such, the goal of our research is the development of an analytical framework for the discovery and characterization of structural alterations using whole genome scans. These scans are high-resolution restriction maps that unambiguously reveal structural details that commonly evade discovery by conventional means such as copy number and cytogenetic analysis.

Oligodendroglioma, a treatable brain tumor, has been selected as a model for understanding the molecular basis of how structural alterations affect measurable phenotypic qualities having important clinical applications. Here, cytogenetic evidence has established that loss of heterozygosity (1p and 19q) is associated with favorable therapeutic outcomes; however, specific molecular candidates are lacking despite ”high-resolution“ analysis of these chromosomal regions using CGH microarrays, FISH, and quantitative PCR of microsatellite repeats.

Since the optical mapping system reveals structural details at the level of a single restriction fragment, this approach is well suited for the identification of the sub-microscopic mutations that lead to treatment responsiveness. Accordingly, a collection of pathologically classified tumors conforming to the 1p/19q paradigm of treatment sensitivity are being analyzed by optical mapping for discovery and characterization of recurrent alterations harboring candidate loci responsible for treatment sensitivity. The elucidation of structural alterations present in oligodendroglioma tumors will not only shed light on the molecular basis for treatment sensitivity, but will also serve as a model system for understanding how this previously unapproachable scale of genomic alteration contributes to disease through mutation and possible genetic diversity.

Nicholas Sanek

“Zic2a and Forebrain Development: Forming a Molecular Model of Holoprosencephaly”

Our laboratory studies the roles of the zic family of zinc-finger transcription factors in the developing zebrafish brain.

Lisa Farmer

“The RAD23 Family of Ubiquitin-Like Proteins Regulates Plant Development and Abscisic Acid Signaling in Arabidopsis thaliana”

The Ubiquitin/26S Proteasome System (UPS) is the preferential mechanism by which transient regulatory or misfolded proteins are discarded. Ubiquitin (Ub) is covalently attached to target proteins by a series of E1-E2-E3 enzymatic activities, and conjugates are delivered to the 26S proteasome, where they are unfolded and degraded. Ub conjugation and proteolysis have been described, but less is known about the identities of specific targets and how they are transported to the proteasome. Evidence suggests that RAD23 proteins are responsible for delivering targets to the proteasome. RAD23s have N-terminal Ub-like (UBL) and C-terminal Ub-associated (UBA) domains that facilitate their interactions with the proteasome and poly-Ub chains, respectively. We predict that these associations allow RAD23s to accept ubiquitin conjugates and then 'dock' with the proteasomal subunit RPN10 to relinquish their cargo. The Arabidopsis RAD23 family includes four highly conserved members. By analysis of genetic knockouts in the four AtRAD23 genes, we found that they are important for appropriate root, shoot and reproductive organ development in seedlings and mature plants, respectively. The AtRAD23s preferentially bind Lys48-linked poly-ubiquitin chains, which are a signature for degradation. They also interact with RPN10, which helps regulate the levels of hormone signaling factors such as the ABA transcription factor ABI5. We have evidence that ABI5 levels are affected by multiple AtRAD23s. Further analysis should reveal other functions of the AtRAD23s, as well as the identities of important developmental regulators that are recycled by the UPS

Jeffrey Berger

“The role of the glutamate receptor clumsy in determining synaptic morphology at the Drosophila neuromuscular junction”

Changes in synaptic morphology in response to experience, the environment, or developmental cues are essential parts of learning, memory and many other behaviors. The Ganetzky lab is using a forward genetic approach to identify genes and molecules involved in determining synaptic morphology at the Drosophila neuromuscular junction. This is an ideal model synapse to study genes that are involved in synaptic plasticity because of its large size, easy accessibility for electrophysiological and immunohistochemical studies, and well characterized morphology. One mutant, 9-76, that was originally identified in a screen for temperature-sensitive paralytic mutants was found to cause overgrowth and hyperbranching at the larval neuromuscular junction. Mapping and complementation tests show that the 9-76 mutant is an allele of clumsy, a gene that encodes an ionotropic glutamate receptor. Clumsy is part of the non-NMDA family of glutamate receptors. Several members of this family are known to be expressed in muscle and are essential for synaptic transmission. However, neuronal expression of wild type Clumsy is sufficient to rescue the temperature sensitive paralysis and neuromuscular junction overgrowth phenotypes of the 9-76 mutant. This evidence suggests that Clumsy may be a neuromodulatory channel that acts pre-synaptically, unlike the other members of the non-NMDA family. Ionotropic glutamate receptors are known to act pre-synaptically in mammalian neurons, but their mechanism of action is not well understood. Further genetic experiments are underway to identify downstream targets of clumsy and elucidate the role that this novel pre-synaptic neuromodulatory ion channel plays in determining morphology at the larval neuromuscular junction.

Andrew Peters

“Testing Population Genetic Models with Caenorhabditis elegans”

University of Wisconsin-Madison

Andy Peter's webpage

Elaine Fuchs

“Stem Cells in Skin”

The Rockefeller University

Elaine Fuch's webpage

Tom Prolla

“Mitochondria1 DNA Mutations, Oxidative Stress and Apoptosis in Mammalian Aging”

University of Wisconsin-Madison

Tomas Prolla's webpage

Alan Templeton

“The Evolution of Humans Over the Past 2 Million Years: Genes, Fossils and Archaeology”

Washington University in St. Louis

Alan Templeton's webpage

Justin Borevitz

“Genomic Approached to the Genetics of Adaptation”

University of Chicago

Justin Borevitz's webpage

Johanne Brunet

“The Impact of Distinct Insect Pollinators on the Movement of Genes Via Pollen”

University of Wisconsin-Madison

Johanne Brunet's webpage

Ilaria Rebay

“Transcriptional Circuitries in Development”

University of Chicago

Elaria Rebay's webpage

Robert Sapolsky

“Stress, Neuron Death, and Strategies for Saving the Endangered Neuron”

Stanford University

Robert Sapolsky's webpage

James Dahlberg

“Maturation and Function of microRNAs in X. laevis Oocytes and Early Embryos”

University of Wisconsin-Madison

James Dahlberg's webpage

Richard Amasino

“Vernalization: Remembering Winter with an Environmentally Induced Epigenetic Switch”

University of Wisconsin-Madison

Richard Amasino's webpage

Dorothy Shippen

“Maintaining An Edge: What Plants Are Revealing About Telomere Biology”

Texas A & M

Dorothy Shippen's webpage

Cori Bargmann

“Assembly of a Behavioral Circuit”

The Rockefeller University

Cori Bargmann's webpage

Gary Roberts

“How Prokaryotes Sense Carbon-Nitrogen Balance, or What Became of Paul Ludden's Graduate Thesis Project? ”

University of Wisconsin-Madison

Gary Robert's webpage

Richard Gourse

“Control of Transcription by Factors That Bind in the Secondary Channel of RNA Polymerase”

University of Wisconsin-Madison

Richard Gourse's webpage

Mark Johnston

“Feasting, Fasting, and Fermenting: Glucose Sensing and Signaling in Yeast”

Washington University in St. Louis

Mark Johnston's webpage