Our overall goal is to understand the mechanisms and principles underlying the robust control of cell division, cell fate, and morphogenesis during animal development. We employ the nematode worm Caenorhabditis elegans as a model for exploring how genetic regulatory networks produce precisely defined temporal and spatial patterns of cell fates regardless of changing physiological and environmental conditions. C. elegans is ideal for studying the genetic and molecular mechanisms for robust control of cell division and differentiation in animal development. This is because the temporal and spatial patterns of cell lineage development in C. elegans are essentially invariant across a broad range of growth conditions, including temperature, nutrient availability, and population density. To better understand this remarkably stress-robust development, we employ C. elegans developmental mutants that exhibit stress-sensitive phenotypes, and we use genetic and molecular analyses of these mutants to identify and characterize genetic regulatory mechanisms that buffer C. elegans development against stress. We particularly address how post-transcriptional gene regulation by microRNAs confers developmental and physiological robustness against environmental change. The expected outcomes of this study include a better understanding of, (from Aim 1) the robust coordination of gene expression programs in early animal embryos, (from Aims 1 and 2) developmental stability in the context of temperature stresses, and (from Aim 3) the global coordination of developmental rate and cell fate specification in the context of changing environmental resources. These outcomes promise to uncover fundamental principles relevant to human biology, including development, cancer, and tissue homeostasis and wound healing.
C. elegans is an excellent system for the genetic analysis of developmental processes in animals, including the control of cell division, cell number, and cellular differentiation. Since many of the proteins and other regulatory molecules that control C. elegans development are also found in mammals, understanding their roles in C. elegans should reveal the mechanisms and principles underlying developmental processes common to all animals, including humans.
|Ambros, Victor; Ruvkun, Gary (2018) Recent Molecular Genetic Explorations of Caenorhabditis elegans MicroRNAs. Genetics 209:651-673|
|McJunkin, Katherine; Ambros, Victor (2017) A microRNA family exerts maternal control on sex determination in C. elegans. Genes Dev 31:422-437|
|Ren, Zhiji; Veksler-Lublinsky, Isana; Morrissey, David et al. (2016) Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans. G3 (Bethesda) 6:1227-37|
|Burke, Samantha L; Hammell, Molly; Ambros, Victor (2015) Robust Distal Tip Cell Pathfinding in the Face of Temperature Stress Is Ensured by Two Conserved microRNAS in Caenorhabditis elegans. Genetics 200:1201-18|
|Ren, Zhiji; Ambros, Victor R (2015) Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress. Proc Natl Acad Sci U S A 112:E2366-75|
|Sterling, Catherine H; Veksler-Lublinsky, Isana; Ambros, Victor (2015) An efficient and sensitive method for preparing cDNA libraries from scarce biological samples. Nucleic Acids Res 43:e1|
|Zinovyeva, Anna Y; Veksler-Lublinsky, Isana; Vashisht, Ajay A et al. (2015) Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal. Proc Natl Acad Sci U S A 112:E5271-80|
|Harandi, Omid F; Ambros, Victor R (2015) Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans. Proc Natl Acad Sci U S A 112:E287-96|
|Nelson, Charles; Ambros, Victor; Baehrecke, Eric H (2014) miR-14 regulates autophagy during developmental cell death by targeting ip3-kinase 2. Mol Cell 56:376-88|
|Zinovyeva, Anna Y; Bouasker, Samir; Simard, Martin J et al. (2014) Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression. PLoS Genet 10:e1004286|
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