Exploring the evolution and interplay between gamma delta T cell receptors and malaria

Malaria is caused by the parasitic pathogen Plasmodium, of which there are 5 known species that infect humans, with P. falciparum the deadliest. The need for an effective vaccine for malaria is now critical. The immune system has co-evolved alongside malaria and is the major target for vaccine strategies. A major hurdle in developing vaccines to malaria has been a lack of understanding of the human immune responses that contribute to natural protection from malaria. This places this project firmly with MRC’s remit to combat infection and the infection & immunity board. Firstly, the concerted evolution of the vertebrate immune system alongside pathogens has ultimately led to two lineages of TCRs in the immune system, and these TCRs drive adaptive immunological memory formation. However, many questions remain as to the specific mechanisms by which pathogens have influenced this evolutionary process. The belief is that the selective pressure of Plasmodium species could have impacted the evolution of the gamma delta TCR in particular. This will be explored using mathematical modelling and bioinformatic approaches. Secondly, the student will have access to human blood samples from individuals naturally exposed to malaria who display clinical resistance. The student will explore the immunological landscape elicited by repeated malaria infection using advanced immunological techniques. Together, this project aims to uncover how gamma delta TCR expression is  skewed by exposure to malaria, and how this and shapes the subsequent immune response to future P. falciparum infection.

Project details

Basic Science
Immunology

Oct 2022 — Sep 2026

United Kingdom