GW4 BioMed3 MRC DLP PhD project: Fat Quality as a Determinant of Cardiometabolic Risk During Ketogenic Diets

About the project

About the Project This project is one of several in competition for funding from the GW4 BioMed3 MRC Doctoral Landscape Programme (DLP), which is offering up to 17 studentships for entry in September 2027. The partnership brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DLP’s website . Please note that the application process may close early to either home or international candidates (or both) before the stated deadline if an unprecedented number of applications are received – check the DLP’s website for details and updates. Supervisory Team: Prof Francoise Koumanov (University of Bath) Prof Javier Gonzalez (University of Bath) Prof Emma Vincent (University of Bristol) Dr Sophie Russel (University of Bath) The Project : Very-low carbohydrate ketogenic diets (KDs) can improve body weight and blood glucose but often raise LDL-cholesterol levels, thereby increasing cardiovascular risk. A key unknown is whether the saturated to polyunsaturated fat ratio in a KD, affects cardiovascular risk. This PhD project will investigate how the fat quality in a KD affects cardiovascular health in a 4-week human trial and gain mechanistic understanding of how the body adapts to such diets using genetic epidemiology and cell culture models. The goal is to determine whether altering fat quality can deliver KD benefits without increasing LDL-cholesterol, improving safety and cardiometabolic health. This forms the basis of the proposed PhD project, which integrates human intervention, mechanistic cell‑culture studies, and genetic epidemiology. Aim and Objectives Aim: To investigate how ketogenic diets affect cardiovascular health in healthy individuals and to uncover the mechanisms by which the body adapts to different fat compositions in KD. Objective 1 (O1): Determine how manipulating dietary fat quality (SFA vs PUFA) within a KD influences cardiovascular risk markers (primary outcome). Secondary analyses will use Mendelian randomisation to assess whether gene expression changes induced by diet causally influence CVD risk. Exploratory analyses will examine sex‑specific responses. Objective 2 (O2): Characterise whole‑body, tissue‑level, and cellular adaptations to different fat qualities within KDs, identifying mechanistic pathways that explain changes in lipoprotein metabolism and metabolic health. Proposed Experimental Plan Human Study (O1) A 4‑week randomised parallel‑group nutritional intervention will be conducted in healthy adults (≥18 years). Measurements will be taken at baseline and after 4 weeks, including physiological assessments, blood sampling, and adipose and skeletal muscle biopsies. Blood plasma and serum will be analysed for insulin sensitivity and cardiovascular risk markers. PBMCs will be isolated to quantify LDL‑receptor transcript and protein levels. Muscle and adipose biopsies will undergo bulk RNA‑sequencing and proteomics to assess expression of metabolic pathways, including LDL‑receptor regulation and AMPK–MNK–eIF4E signalling. Mitochondrial respiration will be measured to evaluate metabolic adaptation to KD. The PhD candidate will contribute to study design, ethics submission, and protocol refinement, with opportunities to tailor aspects of the intervention to their scientific interests. Genetic Epidemiology (O1) Under the supervision of Prof Vincent (University of Bristol), the student will receive training in Mendelian randomisation and genetic epidemiology. They will analyse RNA‑seq data from the human study and integrate these results with large human genetic datasets to test causal relationships between diet‑induced gene expression changes and cardiometabolic outcomes. This training will take place within the MRC Integrative Epidemiology Unit, providing exposure to world‑leading expertise. This component allows the student to shape mechanistic hypotheses based on causal inference, guiding subsequent experimental wor k. In Vitro Cell ‑ Culture Studies (O2) To dissect mechanisms underlying dietary fat‑driven adaptations, the project will use established cellular models representing insulin‑sensitive tissues: adipose, skeletal muscle and liver. These models will be exposed to nutrient conditions mimicking high‑SFA or high‑PUFA ketogenic diets. Analyses will focus on insulin signalling, glucose uptake, lipid metabolism, LDL‑receptor regulation, and broader nutrient‑responsive pathways. This will allow detailed mechanistic interpretation of human findings and help construct an integrated model of how fat quality shapes metabolic responses during KD. The PhD student will have freedom to select specific pathways or hypotheses to pursue, using human and genetic data to refine mechanistic experiments. Across all components, the student will have substantial autonomy to steer the project. They will gain experience in human clinical research, molecular biology, cell culture, transcriptomics, proteomics, mitochondrial physiology, and genetic epidemiology. The project provides a unique interdisciplinary environment bridging nutrition, metabolism, molecular mechanisms, and causal inference. Requirements: Applicants must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second-class degree will only be considered if they have a grade of Merit or above in a master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience. Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath. Enquiries and Applications: Informal enquiries are welcomed and should be directed to Dr Koumanov ( bssfk@bath.ac.uk ) or Prof Gonzalez ( jg833@bath.ac.uk ). Formal applications must be submitted direct to the GW4 BioMed3 DLP using their online application form . A list of all the projects and details on how to apply are available DLP’s website . You may apply for up to 2 projects and submit one application per candidate only. APPLICATIONS CLOSE AT 17:00 (GMT) ON 21 OCTOBER 2026. IMPORTANT: You do NOT need to submit a separate application to the University of Bath at this stage. Equality, Diversity and Inclusion: We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

Research areas