One of the most ubiquitous signaling pathways in the eukaryotic cells is the unfolded stress response (UPR). UPR is crucial for cell survival through enabling real-time adaptive adjustments of the folding capacity in the endoplasmic reticulum (ER). However, UPR hyperactivation caused by severe and prolonged stress, represses the pro-survival response and triggers apoptosis. Not surprisingly, any imbalance in UPR activation may cause several devastated diseases, including cancers and diabetes.
This project focusses on the oldest and most conserved UPR branch, human inositol-requiring enzyme IRE1. The UPR sensor IRE1 is one of the most attractive pharmaceutical targets to cancer research and drug developments (see for example the 2014 Albert Lasker Medical Research Award description). However, the molecular mechanisms of regulation of IRE1 signaling are yet to be discovered. This project will explore how IRE1 mutations associated with different cancers alter IRE1 structure, its activity and cell fate.
This studentship is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. (https://www.whiterose-mechanisticbiology-dtp.ac.uk/). Appointed candidates will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,609 for 2021/22 starts. Awards increase every year, typically with inflation).
UK tuition fees (Around £4,500 per year)
Research Training and Support Grant (RTSG)
Conference and Professional Internships for PhD Students (PIPS) allowances
We aim to support the most outstanding applicants from inside and outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.
We are looking for a motivated PhD student who will exploit a multidisciplinary approach based on state-of-the-art structural biology, computational biology and cellular cancer biology to elucidate the molecular mechanism and contribution of IRE1 mutations to human cancers.