Skip to main content

Elucidating the molecular mechanism of NOD2-mediated autophagy

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.

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology

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
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 199 549,60
Administrative Contact
Stephen Conway (Dr.)