Omer Dushek

The main focus of our research has been to understand how the immune system discriminates between normal and abnormal (e.g. infected) tissues. This job has been delegated to specialised white blood cells called T-cells. These cells patrol the body continuously scanning the surfaces of other cells for protein fragments called antigens. When their T cell antigen receptors (TCRs) bind to even a single foreign-derived antigen (e.g. a fragment from a virus) they initiate immune responses. Their TCR can also bind to highly abundant self-derived antigens (e.g. fragments of our normal proteins) with slightly lower affinity. How do T cells avoid activation when their TCR bind abundant self-antigens, yet respond when they bind even a single foreign-antigen? This is the foundational question underlying our research.

The decision to respond is made by the complicated signalling machinery that integrates signals from the TCR and a host of other, accessory, receptors on the T cell surface.

We use a combination of quantitative experiments and mathematical modelling to uncover the operational and molecular mechanisms underlying signal integration by T cell surface receptors.

A subset of the general paradigms that we work on:
-How T cells discriminate self vs. non-self foreign or neoantigen pMHC (e.g. here).
-How T cells achieve high antigen sensitivity able to respond to even a single pMHC (e.g. here).
-How T cells integrate signals from a host of accessory receptors (e.g. here).
-How T cell activation is achieved by synthetic antigen receptors (e.g. here).
-How the molecular reach of T cell surface receptors and their enzymes impact signalling (e.g. here).
-How T cells implement kinetic proofreading at a molecular level (e.g. here)