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Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Structure and function of the NOD-like receptors NOD1 and NOD2

Research Groupings: Structural and molecular cell biology | Infection and Immunity

Understanding the innate immune system is essential for the development of new therapies for the treatment of microbial infection, the management of autoimmune disorders and the provision of protective immunity via vaccination. My group investigates two members of the intracellular NOD-like receptor family, NOD1 and NOD2. These proteins are activated by fragments of bacterial peptidoglycan; γ-D-glutamyl-meso-diaminopimelic acid for NOD1 and muramyl dipeptide for NOD2.

Leucine rich repeat (LRR) homology models. The LRR region of NOD1 (purple) and NOD2 (blue) were modelled using the human ribonuclease inhibitor complexed with ribonuclease I (pdb 1z7x) as a template

Ligand recognition stimulates receptor oligomerisation and initiates a signalling cascade that ultimately leads to the upregulation of a pro-inflammatory immune response. NOD1 and NOD2 are both associated with a predisposition to inflammatory disorders. The best characterised of these is the role of NOD2 single nucleotide polymorphisms in the inflammatory bowel disorder Crohn’s Disease.

Our work is specifically interested in developing an understanding of how these proteins recognise their bacterial ligands and how they interact with their signalling adaptor molecule RIP2. We are particularly interested in the impact of changes in protein structure on these processes. To achieve these aims we are using a variety of biochemical and biophysical techniques in addition to x-ray crystallography.

Lab members
Joseph Boyle, Sophie Gooch, Chris Howard

References