Genetic Dissection of the Ubiquitin-Proteasome System

A fully funded, three-year PhD studentship is available at the Cambridge Institute for Therapeutic Immunology and Infections Disease (CITIID), where you will work in the Timms Lab using genetic technologies to study the function of E3 ubiquitin ligases.

This studentship project will use the latest genetic technologies to explore the mechanisms through which E3 ubiquitin ligases target their substrates. The ubiquitin-proteasome system (UPS) is the major route through which the cell achieves selective protein degradation, and hence the system plays a critical role in essentially all cellular processes. UPS components are a largely untapped source of potential drug targets, but an enhanced understanding of how E3 ubiquitin ligases select their substrates is required to guide the development of novel therapeutics.

The successful candidate will undertake a three-year research project using a combination of expression screening techniques and loss-of-function CRISPR screening approaches with the goal of (1) identifying substrates of E3 ubiquitin ligases, (2) delineating the specific molecular features ("degrons") that dictate substrate recognition, and (3) exploring how these processes are corrupted in the context of viral infection and autoimmune disease. This studentship is ideal for someone passionate about genetics who is eager to exploit the latest technologies in areas such as CRISPR/Cas9-mediated genome editing, microarray oligonucleotide synthesis, pooled lentiviral library expression screens and next-generation sequencing and associated computational approaches. At the end of the studentship you will have gained a broad range of key experimental and transferable skills, which will provide an effective springboard towards a successful research career in the biological sciences.

You will work in the Timms laboratory, based in the Cambridge Institute for Therapeutic Immunology and Infections Disease (CITIID) which is situated at the heart of the Cambridge Biomedical Campus. The Institute is housed within the brand new Jeffrey Cheah Biomedical Centre, thus benefitting from modern facilities and state-of-the-art equipment. You will also become a member of one of the 31 Cambridge Colleges, through which you will have access to accommodation and a wide variety of student clubs, societies and activities.