Investigating the trafficking and signalling of the pre-T cell receptor complex

这个由MRC资助的博士培训合作伙伴关系（DTP）将尖端的分子和分析科学与数据分析中的创新计算方法结合在一起，使学生能够解决与行业一致的优先领域中的重要应用生物医学研究问题。这是一个为期4年的计划，其第一年涉及一系列教学模块和两个基于实验室的研究项目，导致跨学科生物医学研究硕士学位。前两个学期包括一系列教学模块，让学生在多学科科学中获得坚实的基础。学生还参加了一系列由学术和行业专家领导的大师班，这些专家在分子，细胞和组织动力学，微生物学和感染，应用生物医学技术以及人工智能和数据科学领域。在第三和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。项目：动物从单个细胞发育成为可能包含数万亿个细胞的有机体，这是一项生化编排的壮举，因为它很少出错，因此变得更加引人注目。这一序列的一部分是免疫系统的形成，使动物在暴露于病原体的同时保持健康。T细胞是适应性免疫系统的重要组成部分，其在胸腺中沿着包括几个发育检查点的明确定义的途径发育。这些检查点不仅确保正确的细胞功能，而且通常防止细胞转化为高度增殖状态。然而，在诸如急性淋巴细胞白血病的疾病中，癌性B和T细胞设法破坏这些检查点控制并不适当地增殖。了解这些决策点是如何构建和维护的是基于发现的研究的一个重要目标。然而，这一知识也可以提供新的手段，通过先进的细胞疗法来治疗性地实施这一检查点，这完全属于MRC的职权范围。该项目将探索这样的假设，即在一个这样的发育检查点期间独特表达的前T细胞受体与成熟T细胞受体相比在细胞内被差异性地贩运，并且两种受体之间的这种空间区分是T细胞发育中这个重要决定点的不同结果的分子基础。在进行这个项目的博士生将掌握广泛的生物化学和细胞生物学技术，生物物理学，质谱和生物信息学。

This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project:Animals develop from a single cell to an organism that can potentially contain trillions of cells, a feat of biochemical choreography made more remarkable by how rarely it goes wrong. One part of this sequence is the formation of the immune system that keeps the animal healthy while being exposed to pathogens. T cells are an essential part of the adaptative immune system that develop in the thymus along a well-defined pathway that includes several developmental checkpoints. These checkpoints not only ensure correct cellular function but also normally prevent cells transforming into a highly proliferative state. However, in diseases such as acute lymphoblastic leukaemia, cancerous B and T cells manage to subvert these checkpoint controls and proliferate inappropriately. Understanding how these decision points are constructed and maintained is an important goal for discovery-based research. However, this knowledge could also provide new means to therapeutically enforce this checkpoint through advanced cell therapies, which sits firmly within the MRC remit. This project will explore the hypothesis that the pre-T cell receptor, which is uniquely expressed during one such developmental checkpoint, is differentially trafficked within the cell compared to the mature T cell receptor, and that this spatial discrimination between the two receptors is the molecular basis for the divergent outcomes at this essential decision point in T cell development. In undertaking this project the PhD student will master a wide range of biochemical and cell-biological techniques, biophysics, mass spectrometry and bioinformatics.