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