PhD in T-cell Immunology - Developing a vaccine against Mycobacterium tuberculosis by manipulating Killer T-cell activity.

Background and long-term aim

Our immune system protects us from infectious diseases as well as many forms of cancer. T cells orchestrate this system. The importance of T-cells is evident in HIV/AIDS patients who have lower numbers of these critical cells. The Cardiff University T-cell Modulation Group, headed by Professor Andrew Sewell, has made a number of recent advances in T-cell research, including successfully building T-cells that the HIV virus cannot escape from, using T-cells to successfully fight cancer and building the world’s first ever synthetic non-biologic vaccine. We have also been working on T-cell responses to Mycobacterium, the genus of bacteria responsible for TB. As at Cardiff the necessary facilities and licences are not yet in place to work on M.tuberculosis, we have been focussing on other less dangerous relatives of TB, namely M. smegmatis and M.bovis (BCG), as these bacteria share more than 99% of the same genes with M. tuberculosis. To date we have isolated T-cells that recognise M. smegmatis that seem to be present in most healthy individuals and now wish to extend this research to include M. tuberculosis, where the long-term aim of this project is to develop a novel vaccination approach to combat this global health threat.

Objectives

1. Determine if M. smegmatis reactive T-cells recognise M. tuberculosis-infected cells.
2. If so, we will establish what common molecule they are recognising.
3. If not, we will directly generate killer T-cells that recognise and destroy M. tuberculosis-infected cells and determine what molecule they are recognising.
4. Use the information acquired from objectives 1-3 to perform a pre-clinical TB vaccine study.