The broad goal of this work is to use the C. elegans model system to understand the genetic and molecular mechanisms underlying the developmental regulation of microRNA expression. There are more than 150 distinct microRNA genes in C. elegans, including more than 20 families of microRNAs with homologs in humans. The functions of these are largely unknown, although it is clear that microRNAs play important roles in a wide spectrum of developmeental and phsyiologocal processes in all animals. Little is known about how microRNA gene expression is regulated transcriptionaly or post-transcriptionally by developmental and physiologiical signals. Molecular and genetic approaches will be employed to characterize mechanisms of microRNA transcriptional regulation in C.elegans, and to characterize the proteins and RNA elements responsible for post-transcriptional developmental regulation of microRNA biogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM088365-01
Application #
7698230
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2009-09-24
Project End
2011-08-31
Budget Start
2009-09-24
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$385,596
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
01655
Karp, Xantha; Ambros, Victor (2012) Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans. Development 139:2177-86
Ambros, Victor (2011) MicroRNAs and developmental timing. Curr Opin Genet Dev 21:511-7
Zhang, Liang; Hammell, Molly; Kudlow, Brian A et al. (2009) Systematic analysis of dynamic miRNA-target interactions during C. elegans development. Development 136:3043-55
Hammell, Christopher M; Karp, Xantha; Ambros, Victor (2009) A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:18668-73