Group: The Wülfing laboratory

The research focus of the Wuelfing laboratory is to understand how T cell signalling is amplified or attenuated in health and disease. To gain unique access to the system-wide, complex processes driving such signal tuning, we directly determine signalling as it occurs in time and space inside primary T cells activated by antigen presenting cells with large-scale live cell imaging approaches.

T cells are central regulatory and effector cells of the immune system. A single receptor, the T cell receptor, mediates immunological recognition. However, multiple receptor families then amplify or attenuate the T cell receptor signal to mediate physiological adaptation in health and disease. We investigate the complex signalling processes mediating such adaptation. Understanding how cellular function is regulated in complex signalling networks with dozens of interacting proteins is a critical, general challenge in current biomedical science. A critical component of signalling complexity is that proteins are rarely evenly distributed throughout cells but enrich at particular locations at particular times. At the system scale such spatiotemporal organisation determines how regulatory information flows through signalling networks in time and space. By combining large scale and quantitative live cell imaging of primary T cells activated by antigen presenting cells with the manipulation of spatiotemporal features of signalling intermediates we harness the regulatory information encoded in signalling organisation to understand and control the regulation of T cell function. Thus we address the mutual relation between T cell actin regulation and signalling in costimulation and the tyrosine kinase Itk. We investigate how cytotoxic lymphocytes kill tumour target cells and why such killing is often suppressed inside the tumour microenvironment. We study changes in T cell signalling in the induction of immunological tolerance upon therapy of autoimmune disease. 

The research is described in more detail on our laboratory website http://www.bristol.ac.uk/cellmolmed/research/infect-immune/wuelfing/