Studies on the biochemical modifications regulating initiation, propagation and stabilisation of intracellular signals that modify T cell behaviour.
Description: This programme will study fundamental aspects of T cell activation by bridgingspatio-temporal gaps that restrict our understanding of the T cell "signallingmachinery". Towards this goal, we propose to apply quantitative mass spectrometry and to improve knowledge of post-translational modifications through which proteins convey signals.We will extend our current work on how Tcell antigen receptor (TCR) ligation activates tyrosine kinases during signal initiation by asking how interactions of CD45 with lipid raft resident proteins regulate basal steady-state and TCR signalling.As a continuation of our ongoing efforts to understand how juxtaposed protein arrays mediate signalintegration and propagation, we will seek novel components of TCR- induced signalling complexes and we will determine their spatial organization. Temporal and stoichiometry aspects will be investigated to ask whether TCR "signalosome" acts as a unique entity or as a series of independent ones. Acquisition of a poised cellular state in T cell effectors may require stable post-translational modifications to drive and maintain long-term functional commitment. We have described that CD28 co-stimulation induces arginine methylation of Vav-1 and hypothesised that this modification could be important for commitment. Confirming and extending this idea is the third goalof our programme.
Funder: Wellcome Trust
Amount: £1,935,000
Funding type: grant
Funder scheme: Programme Grant
Start date: 2006-03-01
End date: 2011-06-30
Investigator: Prof Oreste Acuto (lead)
Institution: University of Oxford
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Funded outputs count: 2
Funder award ID: 076558/Z/05/Z
OpenAlex ID: G5407511065