Sarah and Gareth
Sarah Dimeloe and Gareth Lavery

Dr Sarah Dimeloe from the Institute of Metabolism and Systems Research (IMSR) and the Institute of Immunology and Immunotherapy (III), together with Professor Gareth Lavery, also from the IMSR, have been awarded a New Investigator Research Grant from the Medical Research Council for their research interrogating T cell metabolism.

The award, worth more than £800,000 for three years, will fund research investigating new ways to control activity of the immune system in its response to infection as well as in inflammatory and autoimmune diseases such as multiple sclerosis. Current therapies for these diseases are not effective for all patients, meaning that many still suffer with symptoms placing a significant burden on the NHS.

T cells are a critical part of the immune system, protecting people from infections and cancer. However, T cells can also be over-active, which can be harmful. Researchers have recently learned that the activity of T cells is closely linked to a series of chemical processes inside these cells known as metabolism. These processes break down nutrients such as sugar to provide energy and building blocks for the cell. Studies have revealed that patients with infections and autoimmune diseases often have abnormal metabolic processes in T cells.

This research project will test how the production of a molecule called nicotinamide adenine dinucleotide (NAD) is linked to T cell metabolism and both their protective and harmful activity. NAD is produced from vitamin B3 and is required for all stages of the breakdown of sugar and other nutrients in cells. The research group have already identified that when T cells are activated, or switched on, in the laboratory, they turn on enzymes which make NAD from vitamin B3. Additionally, when these enzymes are not active, T cells have much lower rates of metabolism and produce fewer immune signals.

The research group will now build on these observations to understand this in much more depth, using laboratory models of infection and autoimmunity. This will help the research group test whether new drugs targeting this pathway might be helpful in these conditions. Ultimately, the hope is that it may be possible to restore normal safe T cell activity with new drugs, and to better treat inflammatory and autoimmune diseases.

As part of this project, Dr Dimeloe and Professor Lavery will be collaborating with Dr Rebecca Drummond and Dr David Bending, both in the Institute of Immunology and Immunotherapy, and also researchers in the Mitochondrial Profiling Centre and the Metabolic Tracer Analysis Core.

This achievement has been awarded despite the impacts of the coronavirus crisis on research funding and is very much a collaborative achievement across the University of Birmingham. It also highlights the culture of research excellence and long-standing initiatives at the IMSR and III, enabling early career researches to develop to their full potential. Dr Sarah Dimeloe has also achieved this grant whilst working part-time and caring for a young family.