Probing the 4D genome

Programme overview:
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:
How chromosomes are organised within the cells, how this organisation affects gene expression, provides protection for the underlying genetic information and allows correct segregation of chromosomes at mitosis is a fundamental question in cell biology. Although significant progress has been made at the nucleosome and chromatin fibre level, much less is known about how chromatin fibres fold into larger, mega-base domain structures, and how these structures behave in the cellular setting. This project is aimed at probing such chromosome structures using a unique labelling strategy to follow the movements of chromatin domains in living cells. Furthermore, the project will utilise quantitative image analysis combined with mathematical modelling to develop predictive models of the kinetics of chromatin domain movement and reestablishment of domain structure after mitosis.
The project will deliver training in a number of current and emerging techniques to probe the architecture of chromatin in the nucleus. These will include molecular cloning, cell culture, live-cell imagine, quantitative image analysis and mathematical modelling.
The multiplicity of techniques as well as the areas of science these span make the project a perfect fit for the framework of the MRC strategic skill priorities, as these encompass quantitative and interdisciplinary skills, which the MRC deems crucial for the establishment of future research leaders that are able to address issues in areas of unmet national need by employing varied and advanced research skills.