Identification of precision biomarkers for gestational diabetes

Professor Dimitris Grammatopoulos (Warwick Medical School, University of Warwick)
Professor Natasha Khovanova (School of Engineering, University of Warwick)
Dr Harpal Randeva (University Hospital Coventry and Warwickshire)

Between 4-5% of pregnant women in the UK develop gestational diabetes (GDM) due an inability to process carbohydrates properly, leading to high blood sugar. GDM can result in increased risks of problems around the time of birth for both the mother and baby which could be mitigated by early accurate diagnosis. NICE supports risk-based screening for GBD using the 2-hour oral glucose tolerance test (OGTT). However, the exact relationship between the OGTT and pregnancy outcome remain unclear. This PhD project aims to identify biomarkers to improve accuracy of GDM detection by employing state-of-the-art proteomics and lipidomics and advanced data analytics. The student will have access to a large biobank of serum/plasmas of women investigated for GDM with metadata around pregnancy outcomes. The project will explore value of blood molecular and protein biomarkers that cover a wide range of biological functions, including lipid metabolism, insulin sensitivity, dietary intake, chronic inflammation, fluid balance and kidney function. Data from deep biomarker profiling will feed into development of advanced data science knowledge to better characterise disease phenotypes and predict outcomes.

Mechanisms, models and treatment for actin-based human hypertrophic cardiomyopathy

Professor Mohan Balasubramanian (Warwick Medical School, University of Warwick)
Professor Karuna Sampath (Warwick Medical School, University of Warwick)
Professor Faizel Osman (University Hospital Coventry and Warwickshire)

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant condition that has a 50% chance of inheritance. HCM is caused by abnormal thickening and stiffening of the heart muscle which impacts its ability to pump blood around the body. Many patients have no symptoms but, in some patients, the thickened area of the heart muscle can cause scarring that can result in heart rhythm disturbances, shortness of breath, chest pain, palpitation, blackouts and, occasionally, is fatal. Screening for abnormalities in genes that code for important heart muscle proteins can help determine whether someone is at risk of developing HCM. In this project the student will study known HCM causing gene mutations in heart muscle actin genes to examine both the biochemical properties of the proteins and to develop a model system for HCM in the genetically altered zebrafish model to allow us to both study the electrical activity and mechanical function of the diseased heart and assess its response to novel drug treatments. This will enable us to not only better understand inherited human HCM but to develop new treatments for HCM patients.

Improving the therapeutic immunity of cancer vaccines with multi-adjuvant polymeric nanoparticles

Professor Sebastien Perrier (Department of Chemistry and Medical School, University of Warwick)
Dr Shashi Prasad Rama (University Hospital Coventry and Warwickshire)

One of the greatest challenges in current treatments for solid tumours (STCs), including melanoma, breast, liver, lung and head and neck cancers, is preventing tumour recurrence and metastasis, where cancer spreads to other parts of the body. Despite successful initial treatments, many patients experience cancer relapse due to residual tumour cells and an immunosuppressive tumour microenvironment. Cancer vaccines, unlike standard therapies, targets immune cells to enhance antitumour immunity and suppress immunosuppressive cells. This approach reduces the need for frequent secondary treatments, offering a safer, more effective long-term cancer therapy. However, there are side effects associated with the most promising system to date, based on lipid nanoparticle delivery systems, including unwarranted immune responses, as well as cost-effectiveness due to the requirement for cold storage.

The aim of this project is to develop a polymer-based nanovaccine (PNV) using polymeric nanoparticles to deliver adjuvants and antigens. The system will address the issues of current systems by enhancing both specific and nonspecific immune responses, while simultaneously blocking immunosuppressive cells that allow cancer to evade the immune system. This dual action offers a more robust and long-lasting antitumour effect, which we believe will significantly reduce the risk of cancer recurrence and so improve long-term patient outcomes. The project will provide excellent multidisciplinary training in materials science, cell biology, immunology, mouse model systems and preclinical research.