PhD Studentships

We are continuously looking for prospective doctoral candidates to join the lab. If you are interested, please get in touch to discuss all current opportunities for the coming year.

(Bicentenary) Directed evolution approaches to study immune cell receptors

Cell surface receptors are a critical part of our immune system, coordinating cellular responses, communication and movement. The dysregulation of these molecules can cause catastrophic immune failures such as in cancer or autoimmunity, making them highly attractive therapeutic targets. In fact, immune receptors are now amongst the most targeted molecules in the pharmaceutical industry. Nevertheless, we still know very little about how these molecules function and how the genetic makeup of their genes relate to their function. Consequently, there are large portions of immune receptors that have unknown functions because technical limitations constrain systematic explorations of receptor mutants. This hinders our understanding of the immune system and the production of more effective therapies in a wide range of disease settings.

In this project, we will build a synthetic biology platform that allows high-throughput mutational screens of immune receptors targeting endogenous genes. More specifically, we will use directed evolution approaches to systematically edit the nucleotides that make up the DNA sequences of immune receptors and map the functional effect of each mutation within human T cells. This project offers a unique opportunity to develop interdisciplinary expertise across synthetic biology, genomics, immunology, and mathematical modelling, and integrate these fields to develop a novel approach to investigate the fundamentals of immune receptor biology.

Entry Requirements

Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in a relevant subject area. Research experience in molecular biology and/or cell biology is desirable.

https://www.findaphd.com/phds/project/bicentenary-directed-evolution-approaches-to-study-immune-cell-receptors/?p185198

(MRC DTP) Using visible light catalysis for super-resolution mapping of protein-nucleic acid interactors

Understanding the physical distribution of molecules required to drive a biochemical process is essential in understanding how they work. Crucially, mapping the proximity of these biomolecules to one another is central to developing new drugs to treat disease. The technology that underpins proximity mapping methods relies upon the activation of small molecules to form highly reactive intermediates, such as radicals, that form covalent bonds “label” nearby biomolecules. However, these species often diffuse a long way from their source, leading to poor resolution.

This project will build upon recent, cutting-edge advances in synthetic chemistry to generate new, more reactive intermediates, that can label biomolecules with a much higher resolution. This will allow us to precisely map – for the first time – how RNA-binding proteins interact with both proteins and nucleic acids, a crucial missing-link in many drug discovery programs.

As part of this project, you’ll work at the exciting interface of chemistry and biology—designing new chemical methods, synthesizing and characterizing new photocatalysts and probes, as well as developing innovative workflows for RNA–protein studies in collaboration with the Worboys and Ashe groups. You’ll then apply these cutting-edge tools to uncover how RNA-binding proteins control fundamental processes such as protein translation and transcriptional regulation. This PhD opportunity is designed for students with a background in chemistry who are looking to both apply their skills and expertise to solving fundamental challenges in biology and medicine, working alongside world renowned experts at the University of Manchester. No formal biology training is required. This unique project will provide unparalleled experience in synthetic chemistry, structural biology, and medicine.

Entry Requirements 

Applicants should hold (or be about to obtain) a First or Upper Second class (2:1) UK honours degree, or international equivalent, in a relevant subject.

https://www.findaphd.com/phds/project/mrc-dtp-using-visible-light-catalysis-for-super-resolution-mapping-of-protein-nucleic-acid-interactors/?p187099