Benedict Seddon

Professor of Immunology

Research area

T lymphocyte homeostasis and function.

Research programme

Immune regulation

Research summary

T lymphocytes are immune cells that play a central role in regulating immune responses. There are several T cell types, all with different functions, so having the right number and composition of these cells is essential for a normal immunity to infection.

The focus of my group is on understanding the molecular and cellular mechanisms that regulate development and maintenance of mature T cells. We have a particular interested in how developing T cells become fully functional and the mechanisms controlling survival and proliferation once full maturity has been attained.

We use mouse genetics to dissect the signalling pathways and molecular mechanisms regulating T cell development and homeostasis. Currently we are focused in the role of NF-kB signalling, as we have identified a key role for this family of transcription factors for the normal development of T cells. Additionally, we have identified a novel signalling pathway controlling cell death downstream of TNF signalling in T cells. The inhibitor of kappa B kinase complex (IKK) is an essential trigger for NF-kB activity downstream of TNF receptor signalling. We have recently shown that the IKK complex also promotes the survival of T cells in the face of TNF stimulation by directly repressing activity of a key death inducing kinase, RIPK1. Surprisingly, this function does not depend on NF-kB activation. Our future work is focused upon understanding how this pathway is regulated and controls normal T cell function in health and disease.

To gain systems level understanding of complex cellular behaviours of the immune system, we have recently established a temporal fate mapping method that allows us to visualise and investigate the processes underlying tonic reconstitution of the immune system throughout the life course of a host. Employing mathematical analysis is key to understanding and interpreting the data from these experiments. We develop mathematical models of key immunological processes that test our understanding, provide novel insights into systems function and generate new hypotheses that can in turn be tested in the laboratory.