Postdoctoral Research Fellowships in Biology for FY 2009

Goff Loyal A, Cambridge MA

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship for FY 2009. This fellowship supports a research and training plan entitled "Small non-coding RNAs guide epigenetic regulation at target genomic regions" for Loyal Goff. The host institution for this research is Massachusetts Institute of Technology and the sponsoring scientist is Manolis Kellis. Within the eukaryotic cell, including human cells, DNA is densely wrapped around large protein complexes called histones. Various chemical modifications to these protein complexes can determine whether a neighboring gene is turned on or off. This 'epigenetic regulation' by histone modifications is one mechanism by which cells control the timing and synchronization of gene expression. While the proteins that mediate these modifications are well characterized, the ways by which they are recruited to target DNA sequences remains elusive. Recent studies have suggested that small RNA molecules may be involved in regulation of histone modifications. Small RNAs have the potential to interact with histone modifying proteins and scan through the genome to guide these proteins to target specific genomic regions. This research identifies and describes the small RNAs produced during stem cell differentiation, a normal growth process in which dramatic changes in histones take place. The regulation in this system appears to be novel in the way in which the cells turn genes on and off in a coordinated way. The research uses experimental and computational approaches to locate and describe the small RNAs produced during early cell differentiation by searching for regions of intersection between the discovered chromatin-associated small RNAs and specific histone modifications, determined from publicly available epigenomic maps. The training goals are to acquire the computational and informatics skills for the conduct of the research and to provide a solid foundation to begin an academic career that combines computational and experimental biology. Broader impacts include providing both software and data necessary to explore deep sequencing libraries of smRNA sequences and how these sequences affect chromatin availability. There is also a strong focus on teaching and mentoring developing computational biologists.