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.

Adapting the digital endometrial function test (d(EFT)) to predict endometriosis

Dr. Erin Greaves (Warwick Medical School, University of Warwick)
Professor Jan Brosens (University Hospital Coventry and Warwickshire, UHCW)

Endometriosis negatively impacts the lives of approximately 190 million women worldwide, causing debilitating chronic pelvic pain and fertility complications. The disorder is characterised by the growth of tissue like the lining of the uterus (endometrium) outside the uterus, usually in the abdominal (peritoneal) cavity as lesions. Currently it takes on average 8 years for a woman to receive a diagnosis for endometriosis and the current gold standard diagnosis is invasive abdominal surgery (laparoscopy) to visualise lesions. Ultrasound and MRI imaging can aid in the diagnosis of some forms of endometriosis, but the use of these techniques is still limited. This PhD project aims to investigate the applicability of an innovative new diagnostic test currently used for the management of recurrent pregnancy loss, for the diagnosis of endometriosis. The digital endometrial function test ((d)EFT) will be optimised to incorporate endometriosis specific measurements and will significantly advance the field of endometrial diagnostics and improve diagnosis times for endometriosis.

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.