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. .

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM104904-03
Application #
9036276
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Reddy, Michael K
Project Start
2014-06-01
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code