Protein-protein interactions in intracellular signalling View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2001-2015

FUNDING AMOUNT

6371690 GBP

ABSTRACT

To defend ourselves against infection by pathogens our body uses sophisticated mechanisms to detect the presence of pathogens and mount an immune response. It is of fundamental importance that this response occurs in a spatially and timely correct manner as otherwise there is the risk of damage to the host. In fact, improper regulation of immune responses can lead to chronic inflammation and auto-immune diseases and has been linked to cancer. We employ structural and biochemical methods to investigate and describe the three dimensional structure and associated function of proteins that regulate immune responses. The knowledge of such fundamental properties of proteins can help to better understand the cause of disease and might also help to find new drugs against inflammatory disorders and auto-immune disease.| Technical Summary Innate immunity relies on the ability to rapidly detect and eliminate pathogens. This is achieved with the help of pattern recognition receptors (PRRs) that recognise evolutionary conserved patterns specific to a large number of pathogens and initiate a pro-inflammatory response. The pathways transducing these signals need to be tightly controlled to avoid chronic inflammation and auto-immune disease. There is close synergistic interplay between innate and adaptive immunity and the two systems are linked through complex signalling networks. ||Our research is focused on the structural and mechanistic characterisation of protein complexes that regulate signalling in innate and adaptive immunity. We are currently studying members of the NLR (NOD-like receptor) family of intracellular pattern recognition receptors. NLRs respond to the presence of bacteria and endogenous danger signals by triggering the activation of the transcription factor NF-kB and production of pro-inflammatory cytokines. In parallel, we are investigating the role of the IKK complex in the activation of NF-kB, a key regulatory complex on which many immune signalling pathways converge. ||Ubiquitination is a key regulatory signal in immune and inflammatory signalling pathways and we are interested in understanding the molecular details of how this post-translational modification is used to transduce a specific signal. More... »

URL

http://gtr.rcuk.ac.uk/project/4BEA588E-744E-4C11-A967-30C7003F687E

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