1st year MSc (Interdisciplinary Biomedical Research). The student will be assigned to a PhD project prior to the 2nd year of study.

疟疾是由寄生病原体疟原虫引起的，其中有5种已知的物种感染人类，其中恶性疟原虫是最致命的。现在迫切需要一种有效的疟疾疫苗。免疫系统与疟疾共同进化，是疫苗战略的主要目标。开发疟疾疫苗的一个主要障碍是缺乏对人类免疫反应的了解，这种免疫反应有助于自然保护免受疟疾的侵害。这使得这个项目坚定地与MRC的职权范围，以打击感染和免疫委员会。在这个项目中，学生将研究一组知之甚少的T细胞，称为γ δ T细胞。具有某些特性的γ δ T细胞始终与自然感染中的疟疾临床保护相关。我们相信独特的γ δ T细胞受体（TCR）可能是这种保护的关键。跨学科交叉，符合MRC DTP的职权范围，将使学生接触先进的细胞免疫学，生物信息学和数学建模技术。首先，脊椎动物免疫系统与病原体的协同进化最终导致免疫系统中的两个TCR谱系，这些TCR驱动适应性免疫记忆的形成。然而，许多问题仍然是病原体影响这一进化过程的具体机制。我们认为，疟原虫物种的选择压力可能会影响特别是γ δ TCR的进化。这将使用数学建模和生物信息学方法进行探索。其次，学生将有机会获得自然接触疟疾的人的血液样本，这些人表现出临床耐药性。学生将利用先进的免疫学技术探索由反复疟疾感染引起的免疫学景观。总之，该项目旨在揭示γ δ TCR表达如何因暴露于疟疾而偏斜，以及这如何影响随后对未来恶性疟原虫感染的免疫反应。

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.