Structure and cellular function of Tumor Protein D52-like proteins

这个由MRC资助的博士培训伙伴关系（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，使学生能够解决以假设为主导的生物医学研究问题。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：细胞表面表达大量蛋白质。它们利用这些蛋白质来感知环境，粘附在表面和其他细胞上，并四处移动。细胞感知环境和移动的能力部分取决于这些蛋白质在细胞表面展示的数量。这可以通过将新产生的蛋白质放在表面上来控制，其次，通过改变这些蛋白质被带回细胞并随后再循环的速率来控制。以这种方式，这些途径决定了表面上蛋白质的稳态数量，并且在这样做的过程中，决定了细胞响应细胞外信号而检测和移动的能力。细胞运动对于正常细胞功能都是重要的，例如成纤维细胞移动到损伤部位以修复损伤。然而，异常的细胞运动也可能导致疾病。在癌症中，异常的细胞运动性可导致癌细胞远离原发性肿瘤，在其他远端部位引发新的肿瘤，这一过程称为转移。在这个项目中，学生将研究肿瘤蛋白D52样（TPD52）蛋白质家族，这是首次在乳腺癌患者中发现的快速生长的转移性肿瘤。我们最近发现，TPD52样蛋白结合到一类新的纳米囊泡，将其他蛋白质递送到细胞表面。准确了解TPD52样蛋白的作用对于了解它们参与疾病进展非常重要，并可能为未来的治疗提供新的靶点。在这个项目中，学生将研究这些蛋白质的结构，并确定它们如何在分子水平上结合囊泡，以揭示分子作用机制。这将需要一种跨学科的方法，结合细胞成像，结构生物学和生物物理学方法，在原子和细胞水平上可视化这些蛋白质。

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 hypothesis-led biomedical research questions. 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:Cells express a lot of proteins on their surface. They use these proteins to sense the environment, adhere to surfaces and to other cells and to move around. The ability of cells to sense the environment and move is determined in part by how many of these proteins are displayed on the cell surface. This can be controlled by putting newly made proteins on the surface and, secondly, by altering the rates these proteins are taken back into the cell and subsequently recycled. In this manner these pathways determine the steady state number of proteins on the surface and, in doing so, determine the ability of the cell to detect and move in response to extracellular cues. Cell movement is important both for normal cell function, for example fibroblasts move to the site of injury to repair damage. However, aberrant cell movement can also contribute to disease. In cancer, aberrant cell motility can cause cancer cells to move away from the primary tumour to initiate new tumours at additional distal sites, a process known as metastasis. This makes cancer more difficult to treat. In this project the student will study the Tumor protein D52-like (TPD52) family of proteins, which were first identified in breast cancer patients with fast growing metastatic tumours. We have recently found that TPD52-like proteins bind to a new class of nanovesicle which deliver other proteins towards the cell surface. Understanding precisely what TPD52-like proteins do is important to understand their involvement in disease progression and may provide new targets for future therapies. In this project the student will investigate the structure of these proteins and determine how they bind the vesicle at the molecular level to reveal the molecular mechanism of action. This will require an interdisciplinary approach combining cellular imaging, structural biology and biophysical methods to visualise these proteins at the atomic and cellular levels.