Lab focus: Natural and engineered immune receptors

My laboratory studies the structure and function of cellular sensors that direct blood cell development and immune responses. These sensors, also called receptors, receive physiological cues such as growth hormones, stress signals and signs of infection, and translate them into biochemical reactions that drive cellular responses.

We are interested in understanding:

1. how these receptors do their work as biochemical translators of information;
2. what happens when they don’t function correctly, for example cancer, immunodeficiency and other blood diseases; and
3. how we can use this knowledge to build better custom sensors for adoptive cell therapies such as chimeric antigen receptor (CAR) T-cell immunotherapy.

Research interest

We have a particular focus on how the membrane-embedded portions of receptors (transmembrane domains) contribute to the structure and function of immune-signalling complexes. These are not mere anchors for extracellular and intracellular domains, but in fact they provide a unique platform for molecular interactions and represent the only direct physical link between ligand-binding and signalling domains across the cell barrier.

We combine biochemical and biophysical methods (both X-ray crystallography and solution NMR) with protein engineering and cellular and molecular immunology techniques to study the mechanics of receptor activation and the regulation of cell-surface proteins in the immune system. A major focus in recent years has been the development (with computational protein design collaborators) and structural characterisation of synthetic transmembrane domains as tools to control the structures and activities of engineered receptors such as chimeric antigen receptors for CAR T-cell immunotherapies.