Cell-contact dependent regulation of immune cell responses plays a vital role in balancing the need for rapid and efficient responses to a wide variety of pathological challenges, while at the same time maintaining self-tolerance. Over the last decade, our imaging studies – and those of other teams - have helped establish the emerging new paradigm that immune cell activation and inhibition is controlled by transient interactions between supramolecular assemblies of receptors, kinases and adaptors. This is a significantly different concept from a linear cascade of individual protein-protein interactions depicted in textbook diagrams of immune receptor signaling pathways.
The new challenge is to assess the heterogeneity and single-molecule level organisation of protein clusters and understand how this influences signal integration and downstream effector functions. My lab uses high- and super-resolution imaging techniques to reveal novel insights into molecular recognition by human immune cells, and how specific effector functions are realized.
Lagrue K., Carisey A., Morgan D.J., Chopra R., Davis D.M. 2015 Lenalidomide augments actin remodeling and lowers NK-cell activation thresholds. Blood 126, 50-60
Cartwright A., Griggs J., Davis D.M. 2014 The immune synapse clears and excludes molecules above a size threshold. Nature Communications, 5, 5479
Davis D.M. 2014 Presenting the marvels of immunity. Nat Rev Immunol. 14, 351-3
Rudnicka D., Oszmiana A., Finch D.K., Strickland I., Schofield D.J., Lowe D.C., Sleeman M.A., Davis D.M. 2013 Rituximab causes a polarisation of B cells which augments its therapeutic function in NK cell-mediated antibody-dependent cellular cytotoxicity. Blood. 121, 4694-702.
Pageon S., Cordoba S.-P., Owen D.M., Rothery S.M., Oszmiana A., Davis D.M. 2013 Super-resolution imaging reveals nanometre-scale reorganisation of inhibitory NK cell receptors upon activation via NKG2D. Science Signaling, 6, ra62.
Pageon S.V., Aquino G., Lagrue K., Köhler K., Endres R.G., Davis D.M. 2013 Dynamics of natural killer cell receptor revealed by quantitative analysis of photoswitchable protein. Biophys J.105, 1987-96.
Brown A.C.N., Oddos S., Dobbie I.M., Alakoskela J.-M., Parton R.M., Eissmann P., Neil M.A.A., Dunsby C., French P.M.W., Davis I., Davis D.M., 2011 Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy. PLoS Biology,. 9(9):e1001152.