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[
European Worm Neurobiology Meeting,
2009]
Variation in food quality and abundance requires animals to choose whether to stay on poor food patch or wander off in search of better food. Although optimal foraging choice is central to evolutionary survival, the molecular and neuronal mechanisms underlying it are poorly understood. I will present my work on this problem in C.elegans.
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[
Aging, Metabolism, Stress, Pathogenesis, and Small RNAs, Madison, WI,
2010]
My group investigates how RNA signals are transported between tissues and cells in C.elegans. When Fire and Mello reported their discovery of RNAi in C. elegans they also reported that silencing signals spread throughout the animal. These observations suggested the existence of an efficient RNA transport pathway. My lab subsequently identified components of the RNA transport machinery, including a double-strand RNA (dsRNA) channel protein called SID-1and a likely endocytosis RNA receptor called SID-2. SID-1 is highly conserved in nematodes and our analysis indicates that its transport function is highly selective for dsRNA. These observations suggest that SID-1 is under strong selection to specifically transport dsRNA. I will present progress in our efforts to identify and characterize exogenous and endogenous transported RNAs as well as our effort to determine their physiological and/or developmental roles in the worm.
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[
International Worm Meeting,
2021]
Stem cells are unspecialized cells that are able to proliferate to produce more stem cells (mitosis) or differentiate to produce specialized cells. The balance between proliferation and differentiation is controlled by highly regulated signaling pathway(s). The C. elegans germ line is a powerful model that allows genes and pathways that play a crucial role in establishing and maintaining this balance to be identified. The C. elegans gonad contains two gonad arms, where proliferating germline stem cells are located at the distal ends of each arm, while differentiating cells such as sperm and oocyte are located more proximally. The balance between proliferation and differentiation allows this spatial patterning to be maintained in the germline. Recently, our lab has identified the influence of the scaffold protein RACK-1, which is conserved between humans and C. elegans, on the proliferation vs. differentiation pathway. My research is investigating the role of this scaffold protein on maintaining the balance between proliferation and differentiation. A mutation that eliminates
rack-1 results in lowering and mis-localization of the translational repressor protein GLD-1 (Germ Line Defective-1) in the differentiation pathway. Furthermore, loss of
rack-1 results in lower brood size and sterility at higher temperatures. My research seeks to identify the mechanism (either direct or indirect) by which RACK-1 is impacting GLD-1 and furthermore, the differentiation and proliferation decision. My research will provide insight into how stem cell behaviour is regulated in the C. elegans germline.
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[
International Worm Meeting,
2017]
Besides the nuclear genome, eukaryotic cells also contain a circular mitochondrial DNA (mtDNA). mtDNA encodes essential components of the mitochondrial electron transport chain, which produces most of the cellular ATP. Cells typically contain hundreds to thousands of copies of mtDNA. While it is known that the number of mtDNA copies per cell is tightly regulated, the cellular and molecular mechanisms underlying this mtDNA copy number control remain poorly understood. A major difficulty in studying mtDNA copy number control arises from the lack of genetically tractable systems with evidence of robust mtDNA regulation, as well as lack of quantitative methods to accurately determine mtDNA copies. To overcome these challenges, I have developed protocols to accurately and precisely measure mtDNA copy number from single C. elegans individuals at all stages of development. My analyses reveal that the adult C. elegans germline, which harbors most of the mtDNA content, employs active homeostatic mechanisms to regulate mtDNA copy number. In addition, I have discovered that mtDNA encodes a functional feature, which is sensed by the cell to "count" mtDNA copy number. Consistent with this hypothesis, my mutational analysis shows that mutations in mtDNA that disrupt this functional output fail to get counted, resulting in an overabundance of mtDNA copies. Taken together, my results provide fundamental insights into mechanisms of mtDNA copy number control. I am now poised to determine the molecular machinery that counts mtDNA copies, and determine how it is mechanistically coupled with mtDNA replication.
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[
International C. elegans Meeting,
2001]
This abstract is being submitted as a placeholder for a revised abstract to be entered during the week of April 20. This delay is necessary because we would like to include data from different lab personnel, and my rotation students (currently comprising the entire lab) will be making their final lab decisions that week. We are working on several questions regarding chromosome and chromatin remodeling. In particular, we are interested in how chromatin is remodeled during meiosis to accomplish chromosome pairing, crossing-over, and segregation.
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[
Development & Evolution Meeting,
2006]
The adult C. elegans germ line is organized with stem cells at one end and maturing gametes at the other. A single somatic cell, called the distal tip cell (DTC), provides an essential microenvironment or "niche" for the germ line. Our current knowledge of the DTC niche and its control over germline stem cells is the product of many years of work by an ever-increasing and wonderfully active community of scientists. In my talk, I will highlight key advances over the years, our current thinking and major questions for the future.
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[
International Worm Meeting,
2003]
Genome instability and supernumerary centrosomes are characteristic of many tumor cells. To investigate these abnormalities, I am using C. elegans as a model system to study the regulation of microtubule dynamics and centrosome function. My project is focused on AIR-1, a member of the growing Aurora/Ipl1 kinase family. This kinase is associated with mitotic centrosomes, and plays an important role in the formation of bipolar mitotic spindles that can direct accurate chromosome segregation. AIR-1 plays an essential role in centrosome maturation and accumulation of -tubulin. During my postdoctoral training, I would like to identify the cellular partners of this kinase and the regulatory pathway(s) leading to its activation. Two methods will be used to identify these proteins: 1) yeast two-hybrid and 2) solid-phase phosphorylation screenings. These two methods will identify candidates that potentially interact upstream or downstream of AIR-1. The in vivo function of each candidate will be tested by RNA mediated interference (RNAi). The elucidation of AIR-1 regulatory pathway(s) will contribute to our understanding of microtubule dynamics and chromosome segregation in other organisms and may explain the oncogenic power of the mammalian Aurora A kinases.
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[
International Worm Meeting,
2003]
Faced with the task of designing a semester of physiology laboratory exercises in my first semester as an assistant professor, I turned to my research and found what I had always suspected: worms are as wonderful in the teaching laboratory as they are in the research laboratory. As a supplement to several traditional physiology laboratory exercises, for the past two Spring semesters I have required my comparative physiology students to design and implement physiology research projects involving C. elegans. Although I tend to guide the student's projects as little as possible, the level of instructor involvement can be quite variable. By requiring students to write a research proposal prior to initiating their experiments, they can be directed towards realistic projects likely to succeed. The only stipulations were that 1. the research investigate some area of physiology and 2. they not reproduce published data or experiments. At the first laboratory meeting, I introduce C. elegans as a research organism and ask them to consider their favorite area of physiology. From this interest, I guided them towards the relevant C. elegans literature and ultimately to a research plan. Prior to spring break, the students had solidified a research plan that included a hypothesis, a detailed experimental design, and identification of the relevant controls. This way, during the break, I am able to gather the required reagents, strains, and supplies. As the groups begin their experimentation, it is important to regularly check their progress in the event that experimental design troubleshooting is required. Ultimately, the students are responsible for initiating the experiments, limited troubleshooting, data collection, and assembly of the data into a research paper. I required that the research papers adhere to a specific journal format, typically one that is readily available for examples such as Current Biology. In this way, they experience the many steps in the process of converting great research ideas into meaningful publications. In the future, I plan to incorporate peer review into the process by having their papers reviewed by their student peers and other biology faculty prior to completion of the project. At the end of the semester, I also require the students to present their hypothesis, experimental design, data, and conclusions to their colleagues in order to gain experience in oral research presentations and expose all the students to the various research projects. At the meeting, I will present the data collected by four of my undergraduate research teams who investigated many areas of physiology including chemosensory adaptation, learning, and Pseudomonas pathogenecity.
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[
International Worm Meeting,
2007]
Caenorhabditis elegans has proven for many years to be a versatile model for the study of aging and of evolutionarily conserved mechanisms of microbial pathogenesis, among other reasons due to its translucency. The object of my study is the impact of feeding different pathogenic and non-pathogenic Escherichia coli bacteria to C. elegans on the mortality rates of the latter, with particular consideration of late life plateaus (aging deceleration at the population level). I establish kinetics of bacterial proliferation within the worm digestive tract as well as lifespan measurements using killed, fluorescent or knock-out-mutation carrying bacteria.
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[
Mid-west Worm Meeting,
2002]
Faced with task of designing a semester's worth of comparative physiology laboratory exercises in my first semester as an assistant professor, I turned to my research and found what I had always suspected: worms are as wonderful in the teaching laboratory as they are in the research laboratory. As a supplement to several traditional physiology laboratory exercises, this past Spring semester, I required my physiology students to design and implement physiology research projects involving C. elegans. Although I tended to guide the student's projects as little as possible, the level of instructor involvement can be quite variable. By requiring students to write a research proposal prior to initiating their experiments, they can be directed towards realistic projects likely to succeed. The only stipulations were that 1. the research investigate some area of physiology discussed in lecture and 2. they not reproduce published data or experiments. At the first laboratory meeting, I introduced C. elegans as a research organism and asked them to consider their favorite topic from lecture. From this topic, I guided them towards the relevant C. elegansliterature and ultimately to a research plan. Prior to spring break, the students had solidified a research plan that included a hypothesis, a detailed experimental design, and identification of the relevant controls. This way, during the break, I was able to gather the required reagents and supplies. As the groups begin their experimentation, it is important to regularly check their progress in case experimental design troubleshooting is required. Ultimately, the students were responsible for initiating the experiments, limited troubleshooting, data collection, and assembly of the data into a research paper. I required that the research papers adhere to a specific journal format, typically one that is readily available for examples such as Current Biology. In this way, they experience the many steps in the process of converting great research ideas into meaningful publications. In the future, I plan to incorporate peer review into the process by having their papers reviewed by their student peers and other biology faculty prior to completion of the project. At the end of the semester, I required the students to present their hypothesis, experimental design, data, and conclusions to their colleagues in order to gain experience in oral research presentations and expose all the students to the various research projects. At the meeting, I will present the data collected by four of my undergraduate research teams who investigated many areas of physiology including aging, chemosensory adaptation, neurotransmitters, and serotonin modulated behavior.