Scientific Abstract

Proposal No.  LSRF-01
Principal Investigator:  Carrie Rosenberger, Ph.D.
Applicant Organization:  Life Sciences Research Foundation postdoctoral fellowship award to the Institute for Systems Biology (Seattle, Washington, U.S.A.)
Project Title:  Role of endogenous toll-like receptor ligands in inflammatory bowel disease
Period of Award:  June 1, 2005 – November 30, 2007

Innate immunity is thought to play an important role in the initiation and progression of inflammatory bowel disease (IBD).  However, there is little known about the functioning of innate immunity in the gastrointestinal tract.  While IBD is thought to be triggered by the presence of enteric bacteria, repeated studies have been unable to identify specific bacteria in inflamed gut regions of IBD patients.  One possibility is that endogenous toll-like receptor (TLR) ligands may facilitate the progression and chronicity of the inflammatory disease.  Poly(ADP-ribose) polymerase (PARP) is crucial for DNA repair in damaged cells and has been shown to play an important role in IBD models.  Moreover, it activates NF-γB using MyD88, a pathway involved in innate immunity.  This study proposes to assess the role of PARP in TLR-mediated recognition and responses in IBD.