MRC DTP 4 Year PhD Programme: Structural and developmental mechanics in polarized membrane trafficking

This project is offered as part of the University of Dundee 4-year MRC DTP Programme “Quantitative and Interdisciplinary approaches to biomedical science”. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its very high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK. A wide range of projects are available within this programme crossing exceptional strengths in four key areas: Infection and Disease; Responses to Cellular Stresses; Development, Stem Cells and Neurobiology; and Big Data and Translation. All students on this programme will receive training in computational biology, mathematical biology and statistics to equip with the quantitative skills in tackling complex biological questions. In the 1st year, students will carry out 3 rotation projects prior to selection of the final PhD project.

Membranes and their organization are a frontier in our understanding of cell biology. We will focus on polarized trafficking and asymmetric cell division as a model to uncover fundamental mechanisms in biology. The major complexes of these pathways, namely the exocyst and Par complex, may interact. The interconnections of the exocyst with polarized trafficking are well studied, but precisely how the process is regulated is not understood. This project aims to answer mechanistic questions in 1) the regulation of protein structural mechanics in polarized trafficking, 2) and the consequences and fundamental differences in this pathway’s organization between distinct tissues indevelopment. Our philosophy is to address big-picture questions of challenging biology in a hypothesis-driven research project. We take a reconstitution, synthetic biology approach in combination with the powerful tools available for fly genetic and microscopy-based manipulation. This strategy will require combining recombinant protein techniques and biophysical membrane methods with experimental cell biology. We intend to take advantage of developments such as synthetic nanobody libraries and affinity maturation techniques to develop new tools. The combination of these tools with the potential grantedby cryo-electron microscopy provides exciting possibilities for an interdisciplinary project at the state-of-the-art. Moreover, the project will harness the excellent light microscopy and screening platforms available within the University of Dundee.

We are excited to introduce this interdisciplinary research to a highly motivated and ambitious student. The student will emerge a master in state-of-the-art membrane and protein methods, with strong training in developmental cell biology and live-cell microscopy.