Structure and cellular function of Tumor Protein D52-like proteins

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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.