Self-funded MPhil/PhD opportunities in the School of Life Sciences

Salmonella Dublin belongs to non-typhoidal Salmonella that primarily causes self-limiting gastrointestinal illness in humans; however, it has adapted to cause invasive disease and life-threatening infections, especially in elderly people, children, and immunocompromised individuals. The basis underlying the virulence of S. Dublin is not well characterised. Our preliminary data suggest several virulence genes might contribute to bacterial virulence and its ability to evade the immune system; however, no particular genetic determinants were identified to differentiate between invasive and non-invasive S. Dublin strains.

In this project, you will use genomic and transcriptomic approaches to characterize the invasome of S. Dublin responsible for bacterial virulence, identify differentially expressed genes in invasive strains compared with their expression in non-invasive strains and understand the mechanisms used by bacteria to regulate virulence gene expression during its replication inside macrophages.

The project’s findings will enhance our understanding of the basis of virulence in invasive S. Dublin and antimicrobial resistance, ultimately leading to the development of targeted prevention and management strategies, including effective vaccines and novel antimicrobials, which will significantly improve the health and well-being of high-risk individuals and reduce mortality. You should have good laboratory skills in microbiology and/or immunology techniques and demonstrate a genuine interest in next-generation sequencing technologies and associated bioinformatics data analysis.

Please contact Dr Manal Mohammed to discuss: [email protected]

Osteoarthritis is a degenerative disease being a major contributor to long-term disability, leading to increased morbidity and social isolation within groups of individuals over 65 years of age. With over 8.75 million people in the UK experiencing a reduction in quality of life and reliant on current therapeutics that treat aspects of the pathology, but not the underlying causes. The major causal factors of joint injury, obesity and age lead to cartilage degradation with subsequent pain and inflammation occurring via chondrocyte apoptosis and upregulation in catabolic markers of disease.

In this project we intend to explore the role of a key driver of peripheral inflammatory resolution, formyl peptide receptor (Fpr2) in models of chondrocyte activation to ascertain agonist effects on the underlying inflammation and chondroprotection. Utilization of cell lines and primary cells in 2D/3D models using available compounds as well as ones identified from virtual screening libraries will determine the effectiveness of this therapeutic approach.

Please contact Dr Stephen J. Getting to discuss: [email protected]

Within our lab we study human ion channels, mainly potassium channels, that contain genetic mutations which lead to disease states. Understanding ion channel structure in relation to its function allows us to specifically target ion channels to treat certain diseases - also known as channelopathy.

This PhD will utilise a range of electrophysiological techniques to pharmacologically target mutated ion channels and their reverse their functional changes seen within atrial fibrillation. Our lab conducts a variety of techniques including in silico computational modelling, whole-cell patch clamp electrophysiology, cellular fluorescence, confocal microscopy and molecular biology. We work closely with structural biologists, pharmacologists and medicinal chemists to identify novel compounds selective for ion channels.

This project will aim to elucidate potassium channel structure in relation to cardiac disease states and harness this in the development of novel selective compounds. Please contact Dr Kevin P. Cunningham to discuss: [email protected]

Our ageing society is a critical issue. Remaining healthier for longer is a priority with the burden of age-related disease. We want to identify drug targets to develop pro-longevity pharmaceuticals that preserve cognitive function later in life. We will do this by investigating the ways in which the nervous system controls aging and lifespan. The successful applicant will gain skills and experience in areas including:

• genetic screening using C. elegans, an important model organism for the study of aging
• computational methods for protein structure prediction and compound library virtual screening
• assays in human cell culture that enable us to examine aging-related processes.

Please contact Dr Freddie Partridge to discuss: [email protected]