Projects available for 2025 entry
View all Close all
Supervisory team
Project details
Tuberculosis (TB) is one of the of the most prevalent and lethal infectious diseases worldwide, with a third of the world’s population infected with Mycobacterium tuberculosis (Mtb), the causative agent of TB. The rise of drug resistance threatens TB treatment success, with few new drugs in development. Alternative strategies utilising host-directed therapies hold significant promise for patient benefit.
Weight loss is a characteristic clinical feature of TB associated with major changes in metabolism, whilst at the microscopic level, hallmark features include inflammation and tissue remodelling. Adipokines, including leptin (“weight-loss hormone”) and ghrelin (“hunger hormone”), regulate body weight. There is growing evidence demonstrating that adipokines modulate inflammatory and wound healing processes. It is unclear whether adipokines regulate inflammation or tissue remodelling during Mtb infection, representing a new host-directed therapeutic target in TB.
This PhD project offers the exciting opportunity to investigate the effects of adipokines on inflammatory and tissue remodelling responses mediated by fibroblasts and monocytes in TB. The student will integrate into a dynamic research team and use a range of molecular and cellular techniques including cell culture, ELISA, Western blot, qRT-PCR, confocal microscopy and CRISPR-cas9 gene-editing technology. This project will reveal important insights TB immunopathology and identify new therapeutic targets to improve patient outcome.
Skill acquisition
- cell biology techniques including cell culture of primary fibroblasts, monocyte isolation from blood, functional assays such as cell proliferation, migration or collagen deposition assays
- biochemical techniques including Western blot, qRT-PCR and immunofluorescence microscopy
- immunological techniques including ELISA and Luminex multiplex assays
- microbiology techniques including culturing Mtb and how to work safely with a category 3 pathogen
- gene silencing and editing techniques such as siRNA and CRISPR-Cas9
- verbal and written communication skills for scientific and lay audiences
Prior educational requirements
BSc at 2.1 or above or MSc in an appropriate related subject area.
Supervisory team
Project details
Medication use in pregnancy is common and increasing. However, randomised controlled trial evidence on medication safety (to mother, fetus, and baby) is lacking because pregnant women are often excluded from clinical trials. A potential solution is the use of electronic health record data to detect potential harms from medications taken in pregnancy. This pharmacoepidemiology PhD will assess the safety of a selected medications used in pregnancy using NHS data records from primary care (Clinical Practice Research Datalink), hospital admissions (Hospital Episode Statistics) and mortality data from the Office for National Statistics. The medications assessed would be based around a clinical condition of interest to the candidate, on discussion with supervisors. An example would be looking at the safety of different antibiotics for urinary tract infections. The student will work on defining and validating outcomes and then perform statistical analyses to identify risks of adverse outcomes. Potential biases and confounding by indication will be quantified. Candidates will develop their methodological expertise in Health Data Science while answering a clinically important question for the health of mothers and infants.
Skill acquisition
- designing epidemiological studies
- management of large electronic health datasets
- statistical analysis of longitudinal data
- coding in STATA and/or R
- identifying methods to deal with confounding and bias in electronic healthcare record data
- writing papers for publications
- presenting work at scientific conferences
- public engagement for dissemination of research findings
Prior educational requirements
Masters-level training in epidemiology or statistics.
Supervisory team
Project details
Antimicrobial resistant bacteria, and especially the problematic multi-drug resistant (MDR) bacteria, are a threat to all healthcare, limiting our ability to prevent and treat infection. The MDR bacteria that causes the most infection and death globally is methicillin-resistant Staphylococcus aureus (MRSA). MRSA acquire and maintain multiple resistances, even without selective pressure in their natural habitat, typically the colonised human host. While much is known about gene transfer mechanisms, relatively little is known about how AMR gene transfer is controlled, regulated and stably maintained in MDR bacterial pathogens. The aim of this project is to investigate newly discovered genes in MRSA that control the horizontal gene transfer (HGT) and stability of AMR genes.
Skill acquisition
- bacteriology skills
- horizontal gene transfer of AMR genes
- genetic manipulation of bacteria
- bioinformatics
- protein purification
Prior educational requirements
BSc in Microbiology, Infection or similar.
Supervisory team
Project details
Small vessel disease (SVD) is an underlying complication of hypertension and diabetes, presenting in both the brain (cerebral SVD) and heart (cardiac SVD). Mechanistically, SVD causes localised tissue hypoxia by reduced arteriolar blood flow, which increases fibrotic material deposition as organs become maladapted. Understanding novel regulators of fibrosis, therefore, proffers new therapeutic strategies.
Endothelin-1 (ET1) is a potent driver of microvascular disease. Via endothelial cell (EC) ETa receptors, ET1 acutely controls vasoconstriction, with chronic stimulation causing vessel remodelling (medial hypertrophy), cell death, and fibrosis. Our group recently generated genetically modified pigs with inducible over-expression of ET1 (iET1). iET1 pigs mimic human disease; they have increased plasma and tissue ET1 abundance, which correlates with markers of stress and perivascular fibrosis. How ET1 brings about a pro-fibrotic phenotype remains to be explored.
This project seeks to explore the mechanisms by which ET1 causes fibrosis in SVD.
In addition to the transferable skills covered by the graduate school, training in a range of cell and molecular biology, and protein biochemistry techniques focused towards fibrosis and cardiovascular biology will be provided.
Skill acquisition
- design and conduct of scientific experiments
- statistical evaluation of data
- in-depth understanding of signalling mechanisms controlling cellular cross-talk and remodelling
- presentation of scientific data
- time-management and organisational abilities
- management of written records and cross-referencing of electronic data files
- use of computer software for generating research outputs
Supervisory team
Project details
Join this exciting project focused on developing an innovative antibody therapy for breast cancer. While immune checkpoint inhibitors have transformed cancer treatment, their impact on solid tumours like breast cancer remains limited. This project aims to overcome the barriers of the tumour microenvironment by designing an antibody that simultaneously targets a breast cancer-associated antigen and enhances the recruitment of immune cells to the tumour site. By activating the immune system more effectively, this approach has the potential to improve tumour destruction and patient outcomes.
You will gain hands-on experience in antibody engineering, molecular cloning, antibody production in both plants and mammalian cells, along with in vitro cell assays to evaluate the efficacy of this novel therapy. This project provides the opportunity to contribute to the next generation of cancer immunotherapies in a state-of-the-art research environment. It’s ideal for those passionate about advancing cancer treatment and making a real impact in the field of immunotherapy.
Skill acquisition
- molecular biology, DNA manipulation
- agrobacterium transformation and tissue culture of plant and animal cells
- protein purification and affinity chromatography
- immunological, biochemical and optical techniques
- in vitro cell-based assays; flow cytometry
Prior educational requirements
Good BSc degree and/or MRes/MSci in appropriate subject area.
Supervisory team
Project details
Ocular coloboma and microphthalmia are congenital structural malformations of the eyes caused by defective eye morphogenesis during early embryonic stages. These malformations can occur in isolation, in combination, or as part of a broader syndrome, exhibiting considerable genetic heterogeneity. Recent studies have uncovered 21 mutations in the Wnt receptor FZD5 associated with microphthalmia and/or coloboma in humans. Variants are found in all domains of the protein, and there is no clear association between ocular phenotypes and type of mutation.
Only two of the 21 FZD5 variants have been functionally analysed in vitro and in vivo, limiting our understanding of the mechanisms by which those variants lead to the diverse phenotypic outcomes found in patients. This lack of understanding also impacts negatively in our ability to predict the effect of novel mutations in FZD5 or provide genetic counselling.
The aim of this project is to determine the association of selected FZD5 mutant variants to specific phenotypes, by categorising and functionally analysing them.
Skill acquisition
The student will be trained in a wide range of experimental approaches. in vitro and in vivo functional approaches (including embryology, molecular biology, biochemical and cell biology approaches) will be exploited to determine levels of activity of the variants under analysis in cells in culture and zebrafish embryos. This training will provide the student competence in diverse approaches in Biomedical Sciences and awareness of state of the art approaches for functional analysis of human disease genetic variants.
The student will be trained in robust computational analysis for in silico modelling of the variants under analysis. They will also search databases such as the 100K Genome Project and GeneMatcher, to identify further individuals with potentially pathogenic variants in our gene of interest.
Prior educational requirements
A master-level degree and previous experience in molecular biology and laboratory work. Experience in cell biology and/or animal models would be positively considered.
Supervisory team
Project details
This research projects will generate crucial data on the antibody response to Mpox and Ebola infection and/or vaccination in pregnant women in Uganda and lay the foundations for further studies on Lassa and Dengue. In pregnancy, particularly in low-middle income countries, viral infections are associated with adverse outcomes, highlighting the priority of vaccination. However, pregnant women are significantly underrepresented in vaccine studies. The lead supervisor, Professor Le Doare, is at the forefront of maternal vaccination and health policy development at the World Health Organisation and is spearheading Mpox and Ebola vaccine safety and immunogenicity studies in LMICs.
First, the candidate will validate the use of Dry Blood Spot Cards (DBSC) for Mpox and Ebola immunological assays to facilitate sample collection and transport, as an alternative to venepuncture and its limitations (i.e. cold chain). Then, leveraging ongoing Mpox and Ebola vaccine studies, DBSC will be deployed to quantify antibodies titres and their virus neutralising power (Mpox; Ebola), and assess antibodies placental transfer. A systematic review on vaccination in pregnancy will complement and enhance the laboratory component, and inform further studies.
This project suits a resourceful candidate determined to better understand the humoral immunological responses after vaccination in pregnancy and to inform vaccination policies.
Skills acquisition
- This project will allow the student to develop quantitative, laboratory and community engagement skills.
- The candidate will employ advanced statistical methods and analytical skills to develop the systematic review and metaanalysis.
- Through the laboratory component, they will generate immunological vaccine response data and statistical skills will be used to analyse the data.
- The project's interdisciplinary nature is mirrored by the supervisory team, led by an expert in in vaccinology & motherchild immunity and WHO consultant (Prof. Le Doare), an expert in emerging congenital infectious diseases and community engagement (Dr. Sanchez Clemente) and a senior virologist (Dr. Groppelli).
- The project also offers the opportunity to develop and implement communication and collaboration skills between academia and crucial stakeholders in the Ugandan context.
Prior educational requirements
An MSc/MRes in Infection and Immunity or equivalent relevant professional experience will be an advantage.
Supervisory team
Project details
The project offers an excellent opportunity to understand the process of organising and delivering a randomised controlled trial, the research governance, data collection, management, analysis and presentation.
Specific advanced learning objectives may include, but not limited to, stratified analyses, dealing with hierarchical/longitudinal outcomes, time-varying covariates, potential attrition often related with these settings and strategies for missing data in the context of longitudinal clinical trials.
The program will involve working with large data with statistical supervision.
Skill acquisition
The successful student will acquire skills necessary for an independent clinical researcher. The project will offer opportunities to recruit and manage multimorbid, often frail, patients with CKD and heart failure. There will be training on safety monitoring, overall trail management and training of patients and other research staff. The candidate will be working with large datasets and be trained on statistics.
Prior educational requirements
The successful candidate should demonstrate communication skills for patient interaction. Prior clinical research, databases management and statistical experience will be preferred. Undergraduate degree in health sciences is essential.