3.5 Year PhD Leicester Institute for Structural Biology

The Leicester Institute of Structural and Chemical Biology was created in 2016 to bring together established strengths in structural biology, chemical biology and single-molecule research from across the Colleges. The Institute takes advantage of synergies in research technologies and approaches to deliver major advances in both fundamental and translational research.

We have a 3.5 studentship available. Please select from the available projects below before submitting your PhD application.

The four projects available

Project 1 Supervisors: Dr Emma Hesketh and Dr TJ Ragan

Using CryoET and computer science for investigating axoneme structure in PCD

Unleash your potential with this exciting PhD opportunity at the intersection of high-performance computing (HPC), advanced data processing and cryo-electron tomography (cryoET). This project aims to develop an extendable pipeline for managing cryoET processing tools in a HPC environment. The biological focus will be on axoneme structures from Primary Ciliary Dyskinesia (PCD) patient-derived cell lines, to enhance structural data and reveal axonemal disease mechanisms (Walton et al 2023). This interdisciplinary project combines elements of structural biology, computer science and machine learning/artificial intelligence, offering a unique platform to push the boundaries of scientific research. The successful candidate will have access to state-of-the-art cryoEM facilities including Titan Krios electron microscope and a purpose-built GPU based computational cluster/HPC. 

The ideal candidate will have a strong interest in structural biology, should possess or be eager to develop strong programming skills – particularly in Python with a background in biology/biochemistry. 

Project 2 Supervisors:  Dr Fred Muskett and Dr Gareth Hall

Rethinking receptor recognition in cytokines; their role in asthma and inflammation

The ‘four alpha-helix bundle’ cytokines (IL4/IL13 and IL6/IL11) have a broad range of functions and are crucial for fighting infection and the immune response. These cytokines are validated therapeutic targets as their dysregulation results in a broad spectrum of pathological conditions including inflammation (asthma, arthritis), sepsis and cancer.

Our previous studies of IL13 and IL6 (DOI: 10.3389/fimmu.2023.1216967) have indicated that they, and related cytokines, exist in at least two states – receptor competent and incompetent. This equilibrium state provides a new insight into the differing receptor signalling complex formation. We will use a combination of NMR spectroscopy, computational methods and functional assays to interrogate these conformations, enhancing our understanding of receptor recognition and protein-protein interactions in general. With this knowledge, the potential for the development of small molecule allosteric inhibitors that can trap the cytokine in an ‘incompetent’ state could be realised.

Project 3 Supervisors: Dr Gareth Hall and Dr Fred Muskett

Investigating TNF-Alpha Multimerisation and Activation Mechanisms

Tumour necrosis factor-alpha (TNF-α) is a key cytokine in immune regulation and inflammation, existing as a transmembrane precursor that undergoes proteolytic cleavage to release a soluble form. Both membrane-bound and soluble TNF-α exert their effects by binding TNF receptors (TNFR1/2), initiating signalling cascades that regulate cell survival, apoptosis, and inflammation. However, the structural dynamics of TNF-α multimerization and its impact on receptor activation remain poorly understood.

This PhD project aims to dissect the molecular mechanisms governing TNF-α multimerization and its functional consequences on TNFR activation. Using biophysical techniques such as NMR and crystallography, along with cellular assays and computational modelling, the study will elucidate how TNF-α oligomerization influences receptor binding and downstream signalling. Understanding these processes could reveal novel therapeutic options for TNF-driven diseases, including autoimmune disorders and cancer. This project integrates structural biology, immunology, and drug discovery approaches to advance TNF-targeted therapeutics.

McMillan, D., Martinez-Fleites, C., Porter, J. et al. (2021) Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF. Nat Commun 12, 582. doi.org/10.1038/s41467-020-20828-3

Project 4 Supervisors: Dr TJ Ragan and Dr Emma Hesketh

Computational CryoET: AI, UI & HPC-Powered Research

A PhD opportunity is available at the intersection of high-performance computing (HPC), data science, and cryo-electron tomography (cryoET). This interdisciplinary project integrates structural biology, computer science, and AI/ML to develop tools for 2D and 3D image processing and analysis.

The project focuses on axoneme structures from Primary Ciliary Dyskinesia (PCD) patient-derived cell lines. The candidate will have access to state-of-the-art cryoEM facilities, including a Titan Krios microscope, a GPU-based computational cluster, and national HPC resources.

Ideal candidates should have strong Python programming skills and enthusiasm for AI/ML in biomedical science. Experience in image processing is beneficial but not required; wet lab experience is desirable but not essential.

This PhD offers excellent career development opportunities, including training in cutting-edge AI and computational techniques, collaborations with leading researchers, and potential for high-impact publications. Graduates will be well-positioned for careers in academia, biotech, or AI-driven healthcare industries. We encourage interested candidates to get in touch and apply.

Please refer to the application and funding information below before submitting your application using the link at the bottom of the page.