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Control of T cell activation by co-signalling receptors

Sir William Dunn School of Pathology

Dr O Dushek Friday, January 08, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

T cells orchestrate immune responses crucial for the elimination of infections and cancers. They do this by initiating a diverse set of effector responses when their T cell surface receptors (TCRs) recognize these threats. It is now appreciated that a large number of other co-signalling receptors shape these responses. Indeed, the remarkable clinical success of checkpoint inhibitors and chimeric antigen receptors is based on perturbing co-signalling receptors. But these therapies have also highlighted that our understanding of how they shape T cell responses is limited. This is exemplified by our crude binary classification of them into stimulatory or inhibitory receptors (see for example Chen & Flies (2013) Nature Reviews Immunology). A key aim of the laboratory is to discover how these co-signalling receptors differentially regulate the quantitative T cell response to antigen and in this way, we aim to move the field beyond the binary classification of these receptors. We exploit this new information in the rational design of T cell based therapies.

The DPhil project will involve experiments with primary human T cells and biophysical analysis of receptor/ligand interactions. We are focusing on a number of receptors within the immune receptor group and tumour necrosis factor receptor super-family. In addition to a variety of experimental techniques, the project will also involve mathematical models.

Depending on the experience and interest of the student, there is flexibility in the focus of the project.

Funding Notes

4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£17,285 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
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