ºÚÁÏÉç

Cell fate outcome, whether a cell lives or dies, is determined at the molecular level by numerous regulatory proteins including some beyond standard apoptotic pathways. BMX tyrosine kinase is one of these regulatory proteins, whose activity simultaneously promotes cell proliferation and inhibits commitment to apoptotic cell death. However, the mechanism by which BMX is activated, regulates its cellular localisation, and interacts with its apoptotic substrates remains unknown. BMX is a multi-domain protein containing an N-terminal PH domain which binds to cellular membranes to facilitate cell signalling events and act as a scaffold to bring multiple binding partners into close association to increase signalling efficiency and function. The PH domain of BMX is frequently mutated in Cancer. This project will therefore first analyse the BMX PH domain to identify the regions required for both protein and lipid binding to characterise the role the PH domain plays in regulating BMX activity in response to cell signalling events and cellular localisation. Secondly, the impact of Cancer relevant mutations within the PH domain on lipid and substrate binding will be established using biochemical, structural biology and cell biology techniques. Thirdly, structure-driven drug design will be used to identify molecules to modulate protein/lipid binding and evaluate BMX PH domain as a novel therapeutic target in Cancer.

For subject specific enquiries please contact: j.fox3@hud.ac.uk.

The rise of antimicrobial resistance (AMR) in bacteria is a growing global health crisis. By 2050, it is projected that AMR-related deaths will surpass cancer as the leading cause of global mortality. The process of developing a drug, from initial discovery through to regulatory approval, is estimated to take ~10–15 years and cost ~$2–3 billion. One potential avenue to be explored is drug repurposing, this selects for pre-existing FDA approved drugs (which have already been approved for medical use) with serendipitous antimicrobial activity. Drug repurposing significantly reduces both the financial and temporal costs of drug development. Globally, infections are observed in 26.9% of patients with burn wounds (with 42-65% of deaths attributed directly to infection). Key bacterial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa drive pathogenesis, resulting in polymicrobial biofilm formation, and enhanced resistance to current treatments. This project aims to:

1. Identify novel therapeutic agents with antimicrobial activity against burn-wound associated bacterial pathogens
2. Develop a biofilm model which is more physiologically relevant of the polymicrobial nature of burn wounds and
3. Incorporation of lead candidate drugs into hydrogel coatings and efficacy testing against human epithelial cells and a porcine burn wound model.

For subject specific enquiries please contact: a.j.slate@hud.ac.uk.

Wound healing is a complex biological process involving multiple skin cell types. While fibroblasts and keratinocytes have been extensively studied using 2D and 3D models of wound healing, the roles of other skin cells - such as melanocytes, adipocytes, and endothelial cells in such models remain underexplored.

This PhD project explores how overlooked skin resident cell populations influence wound healing at the tissue level. You’ll work with plastic surgeons and access healthy human skin donated from routine procedures (including abdominoplasties, breast reductions, and graft surgeries). Using this material, you’ll isolate primary human skin cells and engineer advanced 3D skin models by repurposing the dermis as a biological scaffold. This is a rare opportunity to combine clinically relevant human tissue, cutting edge bioengineering, and fundamental cell biology to uncover mechanisms that could transform future wound repair therapies.

By highlighting the contributions of these cells, we seek to expand the current understanding of skin regeneration and identify novel cellular targets that could be leveraged in advanced wound care strategies. These findings may inform the development of next generation dressings and therapeutic interventions designed to accelerate healing and improve patient outcomes. Additionally, this work will lay the foundation for a new 3D model system capable of studying the interactions and functions of diverse skin cell types in the wound healing environment.

Finally, developing a reproducible in vitro wound healing model will reduce reliance on animal testing, aligning with the 3Rs - Reduction, Replacement, and Refinement. This model will provide a human relevant platform for evaluating novel therapies, accelerating preclinical research while promoting ethical and translationally meaningful outcomes.

For subject specific enquiries please contact: k.bertal-ngaage@hud.ac.uk.

The neovascular form of age-related macular degeneration (nAMD) can have devastating effects on central vision, but fortunately timely intervention with anti-vascular endothelial growth factor (antiVEGF) has improved outcomes for countless individuals. In the UK NICE guidelines recommend treatment commences within 14 days of referral to the hospital eye service. A recent study found that the optometric referral accuracy of nAMD may be as low as 37%, a figure which has not improved in over a decade. This could result in many false positive referrals – patients suspected of having nAMD when they do not actually have it, possibly leading to treatment delays for those with the disease. In Bradford for example, only one fifth of suspected nAMD patients are seen within the recommended 14 days. This PhD project will aim to investigate factors that may influence optometric referrals of nAMD, including the use of optical coherence tomography (OCT) imaging, and look at possible ways of improving diagnostic accuracy. Depending on the interests of the candidate this could be through focus groups / questionnaires / semi-structured interviews or through the development of a training tool for primary care clinicians.

For subject specific enquiries please contact: c.fulcher2@hud.ac.uk.