Grant: CAG/CCFC/CIHR Summer Studentship for Research in Gastroenterology

Nod proteins belong to a class of ¿pattern recognition molecules¿ called Nod-like receptors. Nod1 and Nod2 are the best characterized of these molecules. These proteins in the host are capable of recognizing bacterial infection through their detection of a component of the bacterial cell wall called peptidoglycan. Once triggered by this bacterial product, Nod proteins commence a pattern of gene expression in cells that helps to clear infection. Nod2 has been recognized as an important mediator of inflammatory induction since the gene encoding Nod2 was the first susceptibility gene identified for the chronic inflammatory bowel disease, Crohn's disease. How this mutation influences the development of disease remains unknown. Our recent findings point to the idea that defective Nod2 signaling leads to hyper-responsiveness of the intestinal mucosa to bacteria that make up the normal flora. Specifically, findings from our laboratory show that Nod signaling, in addition to triggering inflammatory pathways, homeostatically controls immune responsiveness. Therefore, lack of Nod-driven signals prevents the development of a normally tolerogenic environment vis-à-vis the colonic flora. Uncontrolled inflammation at the level of the intestinal mucosa thereby ensues. The basic and fundamental studies described in this project, which are aimed to define these Nod-dependent processes that control mucosal homeostasis, will certainly give new insight into their implication in the pathogenesis of Crohn¿s disease. Furthermore, these studies may open up new avenues for the treatment of this disease through the modulation of Nod function.