Investigating the trafficking and signalling of the pre-T cell receptor complex
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
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.
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.
