The function of NOD2 in health and Crohn's disease

The intracellular pattern-recognition receptor NOD2 is essential for defence against intracellular microbes, and polymorphisms in NOD2 are associated with the development of the inflammatory bowel disease Crohn's. Professor Simmons has shown that NOD2 activates autophagy to destroy intracellular microbes in a pathway that is defective in Crohn's disease, via the mitochondrial fission protein Drp1. She has three major aims in investigating aspects of NOD2 function: to define signalling to Drp1 with a view to understanding the mechanism of NOD2-mediated Drp1 activation, and to define targets for enhancement of this activity in Crohn's; to understand the influence of NOD2 on antigen presentation and the differences in T-cell responses to different commensal microflora in Crohn's; and to understand the role of NOD2 function in intestinal epithelial cells and how Crohn's-variant NOD2 affects intestinal barrier health.