Signalling in T-cell immunity (360G-Wellcome-060111_B_99_A)

£320,175

An immune response against opportunistic infections, foreign transplants and in autoimmune disorders is critically dependent on the generation of intracellular signal by the antigen-receptor (TcR?/CD3) and the co-receptors (CD28, CTLA-4) on the surface of T-cells. Key mediators of signalling include CD4/CD8-p56lck complexes, the tyrosine kinase ZAP-70 and a novel family of immune specific adaptor proteins. In this application, we propose to extend our studies on the nature of protein-tyrosine kinases and adaptors that regulate cytokine production in T-cells. Specifically, we propose to focus on the adaptors FYB and SKAP-55, their phosphoryation sites, interactions with other proteins, nuclear vs. cytoplasmic function and their regulation of thymic differentiation and peripheral T-cell function. Likewise, we propose to elucidate the molecular mechanisms that regulate CD28 positive vs. CTLA-4 negative signalling, and their connection with the TcR?/CD3 complex. Ultimately, we hope to provide insights that will allow for the development of therapies designed to enhance immune responses against infectious agents, and dampen inappropriate responses in autoimmune disorders.

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Grant Details

Amount Awarded 320175
Applicant Surname Rudd
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2010-06-10T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Principal Research Fellowship Renewal
Internal ID 060111/B/99/A
Lead Applicant Prof Christopher Rudd
Partnership Value 320175
Planned Dates: End Date 2012-11-30T00:00:00+00:00
Planned Dates: Start Date 2010-12-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Andrew Wyllie