The first target in the Program in Immune Diseases is Inflammatory Bowel Disease (IBD). IBD is comprised of at least two clinically and mechanistically distinct components, Crohns Disease (CD) and ulcerative colitis (UC). Understanding the causes of IBD is further complicated by complex genetic associations with disease as well as the contribution of environmental factors. Both of these, in turn, may impact on the highly intricate, poorly understood and biologically potent bacterial community of the intestine referred to as the microbiome. Finally, the active and passive interaction of these diverse factors with cells of both the innate and adaptive immune system, and the role of the immune system in disease initiation and propagation, is only nominally defined.
The goal of this Program is to develop novel strategies for target discovery in IBD, with a focus on identifying key events in adaptive and innate immune responses to colonic bacteria. Like other AMRF Programs, this strategy will entail a thorough evaluation of normal tissues and those from affected and unaffected intestinal sites of patients. Evaluation of these tissues will help identify novel targets for intervention. We will bring together outstanding researchers and physician-scientists who will share their expertise in diverse areas. The strategy will include (i) a thorough and integrated evaluation of patient samples which will allow for better patient stratification and treatment as well as provide mechanistic insights into human disease, (ii) constructing new preclinical models of IBD in mouse (and perhaps invertebrates) to more faithfully model human disease, (iii) creating tools and strategies to better understand the control of intestinal epithelial activity and the role of the microbiome in health and disease, and (iv) identifying novel genetic linkages and therapeutic interactions to provide new approaches to preventing or ameliorating IBD.
The proposed structure of the IBD Program is envisioned along the following lines:
RESEARCH HUBS/ COLLABORATIVE PLATFORMS -
Research Hub A: Longitudinal Study of Ulcerative Colitis and Crohn's Disease Patients
Research Hub B: Systems Biology
Research Hub C: Mouse Models with Mutations of GWA-implicated IBD Susceptibility Genes and Nominated Immune Response Genes; Studies in Germ Free Mice
INTERACTIVE RESEARCH PROJECTS -
Project 1. In vivo and in vitro Models of Epithelial Function
Project 2. Strategies for Developing Therapeutic Agents
Project 3. Microbial Communities in Patients