An 'unconventional' approach to the COVID 19 pandemic: the role of T cells in virus recognition

这个充满活力的项目将汇集两个已建立的小组，研究针对SARS-CoV-2的非常规免疫反应的潜在关键作用。对covid - 19大流行的反应迅速，并导致成功开发了针对病毒刺突蛋白的疫苗。虽然这对covid - 19产生了重大影响，但它也强调了基于spike的疫苗的特异性也可能是它们的致命弱点。事实上，持续的全球病毒传播已导致变异的出现，由于流行的刺突序列与用于疫苗的序列不匹配，这些变异可使疫苗规划失效。因此，研究与病毒序列无关的策略是至关重要的。这个令人兴奋的项目将研究先天免疫反应对抗病毒性疾病的潜力，以及非常规T细胞（即T细胞）如何通过识别这些细胞表达的“危险信号”对感染细胞做出快速反应。该项目特别提出了三个相关但独立的问题：1。是什么信号在被感染的细胞上触发了非常规T细胞的这种快速“检测和杀死”方法？2. 在非传统的T细胞中，是什么分子机制解开了“检测和杀死”的方法？3. 感染SARS-CoV-2的非人类灵长类动物的组织中是否存在危险信号和反应？该项目将需要广泛的技术，包括细胞培养（细胞系，原代细胞），流式细胞术，western blotting；与具有复制能力的SARS-CoV-2 （sgl的BSL3遏制实验室）合作。SARS-CoV-2非人类灵长类动物组织的免疫组织化学和原位杂交将在英国卫生安全局（Porton Down）的比较病理学团队进行，成功的申请人将在那里度过3个月（实习）。这个项目适合自我激励的人，有很强的学习和交付意愿。你将对免疫学及其对全球健康的影响有浓厚的兴趣，并对解决问题有积极的态度。

TBCThis dynamic project will bring together two established groups to investigate the potentially crucial role of non-conventional immune responses to SARS-CoV-2. The response to the COVID19 pandemic has been rapid and has led to the successful development of vaccines that target the viral Spike protein. Whilst this has had a substantial impact on COVID19, it is has also highlighted that the specificity of Spike-based vaccines might also be their Achilles heel. Indeed, sustained world-wide virus transmission has resulted in the emergence of variants that can render the vaccine programmes ineffective due to mismatch between the circulating Spike sequences and those used for the vaccines. It is therefore crucial to investigate strategies that are independent of virus sequences. This exciting project will investigate the potential of the innate immune response against viral diseases and how unconventional T cells (i.e. T cell) respond rapidly to infected cells by recognising 'danger signals' expressed by these cells. In particular, the project asks three related but free-standing questions: 1. What are the signals on the infected cells that trigger this fast "detection and kill" approach by unconventional T cells? 2. What are the molecular mechanisms that unravel within unconventional T cells to generate that "detection and kill" approach? 3. Are danger signals and responses present in tissues from SARS-CoV-2 infected non-human primates? The project will require a wide range of techniques including cell culture (cell lines; primary cells), flow-cytometry, western blotting; work with replication competent SARS-CoV-2 (BSL3 containment laboratory at SGUL). Immunohistochemistry and in situ hybridisation of SARS-CoV-2 non-human primate tissues will be undertaken at the Comparative Pathology team at UK Health Security Agency (Porton Down), where the successful applicant will be expected to spend 3 months (placement). This project suits a self-motivated person with a strong will to learn and deliver. You will have a strong interest in immunology and its impact in global health, coupled with a pro-active attitude to problem-solving.