Objective NOD2 is an intracellular pathogen recognition receptor (PRR) expressed in monocyte lineage and intestinal epithelial cells. NOD2 recognizes muramyldipeptide (MDP), a component of bacterial cell walls and MDP stimulation induces a signalling cascade that synergises with that of other PRRs to mature dendritic cells (DCs) and renders them competent for antigen presentation. NOD2 is notable in that variants of the receptor are associated with 40% of western Crohn’s (CD) disease. Previously Dr Simmons group has shown that NOD2 induces autophagy in dendritic cells and that this is required for correct antigen presentation and bacterial handling. CD patient DCs expressing variant NOD2 show defective autophagy induction, impaired bacterial handling and antigen presentation. This combination of effects could predispose to inflammation by allowing abnormal persistence of bacterial components in the mucosa. Here, the aim is to investigate the mechanism of NOD2-mediated autophagy and to examine NOD2 interacting proteins pre- and post- stimulation with MDP. Furthermore, siRNA library screening will be used to identify genes that participate in the NOD2 autophagy pathway. Elucidating the special features of NOD2-mediated autophagy is essential to develop targeted immunomodulators of this pathway. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2010-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Address Wellington square university offices OX1 2JD Oxford United Kingdom See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Administrative Contact Stephen Conway (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
