Molecular mechanisms of leukocyte recognition
Research type
Research Study
Full title
Molecular mechanisms of leukocyte recognition
IRAS ID
212878
Contact name
Omer Dushek
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Duration of Study in the UK
9 years, 11 months, 31 days
Research summary
Leukocytes are white blood cells that continuously patrol the body for abnormal infected or cancerous cells. They do this using a large group of surface receptors that collectively recognise patterns of ligand proteins expressed on these other cells. The integrated signals from these surface receptors determines whether a leukocytes will be activated to respond to eliminate a threat. For example, the T leukocyte or T cell can initiate and regulate adaptive immune responses by the integrated signals from its T cell antigen receptor and a host of co-stimulation (e.g. CD2, CD28) and co-inhibition (e.g. BTLA, PD-1) receptors. Given the importance of leukocyte activation in both helpful (cancer, infection) and unhelpful (autoimmunity, allergy, transplants) immune responses, their surface receptors are attractive therapeutic targets. Although a number of therapies are already approved, they often exhibit toxicities that can limit their use.
Individually, these surface receptors have been extensively characterised at the molecular level, but we have less information about how they integrate their signals with each other and how this controls leukocyte activation. Therefore, improving this understanding can be used to improve the design of therapies. This project aims to use physiologically relevant human leukocytes to systematically study the molecular mechanisms and functional consequences of signal integration by surface receptors. To do this, we will systematically present ligands to primary human leukocytes and study their activation status. Mathematical modelling will be used to understand mechanism and design improved therapies.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
20/EM/0267
Date of REC Opinion
30 Oct 2020
REC opinion
Favourable Opinion