The broad goal of this work is to use the C. elegans model system to understand the genetic and molecular mechanisms underlying how microRNAs mediate organismal responses to the nutitional and pathogenic properties of an animal's diet, and help confer developmental and physiological robustness against environmental change. There are more than 150 distinct microRNA genes in C. elegans, including more than 20 families of microRNAs with homologs in humans. Although it is clear that microRNAs play important roles in a wide spectrum of developmental and phsyiological processes in all animals, the functions of these microRNAs are not well understood in detail. Nor is it well understood how microRNA gene expression is regulated transcriptionally or post-transcriptionally by developmental and physiological signals. Molecular and genetic approaches will be employed to produce a comprehensive, genome-wide analysis of microRNA gene regulatory networks in C.elegans, with an emphasis on identifying microRNAs that mediate responses to the nutritional and pathogenic qualities of the animals'bacterial diet diet. In depth functional analysis will be conducted for a set of specific evolutionarily conserved microRNAs that are known to act in pathways that confer developmental and physiological robustness in the context of changing dietery conditions. .
The coordination of developmental, metabolic, and stress response gene expression programs is fundamental to how multicellular organisms survive in changing environments, and for the mechanisms underlying a wide range of diseases, including cancer, metabolic syndromes, and diabetes. The C. elegans model will be employed to study the genetic regulatory mechanisms underlying these phenomena.