Exploring the evolution and interplay between gamma delta T cell receptors and malaria
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
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.
In this project, the student will study a poorly understood group of T cells, called gamma delta T cells. Gamma delta T cells of certain properties consistently correlate with clinical protection from malaria in natural infection. We believe f the unique gamma delta T cell receptor (TCR) may be critical to this protection.
The interdisciplinary crossover, fitting with the MRC DTP's remit, will expose the student to advanced cellular immunology, bioinformatics and mathematical modelling techniques.
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. We believe 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 are skewed by exposure to malaria, and how this and shapes the subsequent immune response to future P. falciparum infection.
In this project, the student will study a poorly understood group of T cells, called gamma delta T cells. Gamma delta T cells of certain properties consistently correlate with clinical protection from malaria in natural infection. We believe f the unique gamma delta T cell receptor (TCR) may be critical to this protection.
The interdisciplinary crossover, fitting with the MRC DTP's remit, will expose the student to advanced cellular immunology, bioinformatics and mathematical modelling techniques.
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. We believe 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 are skewed by exposure to malaria, and how this and shapes the subsequent immune response to future P. falciparum infection.
Organisations
People |
ORCID iD |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/W007053/1 | 30/09/2022 | 29/09/2030 | |||
| 2730187 | Studentship | MR/W007053/1 | 02/10/2022 | 29/09/2026 |