The six projects for the current call are listed below. The application form will ask for one project to be selected or two projects to be ranked in order of preference.
Project title: Unlocking the promise of DNA vaccines
Lead supervisor: Dr John Tregoning
DNA vaccines are an extremely exciting platform with significant potential for protection against both existing and emerging infections. The partner company for this project, Touchlight Genetics, has developed a cell free platform capable of producing extremely large quantities of synthetic DNA that could be used to control an emerging pandemic infection, for example against influenza which poses a significant global health threat. However, the full promise of DNA vaccines has yet to be achieved, with DNA vaccines underperforming in clinical trials to date. The project will use cutting edge tools in formulation, vaccine design and immunology to optimise DNA vaccines and realise their full clinical potential. The objectives of the project are: Year 1: Use Touchlight’s technology platforms to alter the expression and immunogenicity of DNA vaccines in vivo. Year 2: Design and test novel influenza DNA vaccines with increased breadth and coverage. Year 3: Investigate how DNA immunisation can prime the immune system to respond better to other vaccine platforms. The student will develop skills in informatic analysis of antigens, in vivo vaccination and challenge studies, DNA manufacture and formulation as well as working with the commercial development unit at Touchlight Genetics to better understand the route to product development.
Project title: Optimising antimicrobial prescribing through bio-sensor guided precision prescribing
Lead supervisor: Professor Alison Holmes
This is an exciting opportunity to directly improve patient care and address the threat of antimicrobial resistance (AMR) as part of a larger multidisciplinary collaborative research project aimed at developing novel, innovative bio-sensors to optimise antimicrobial therapy. AMR is considered to be one of the most pressing risks to global health and threatens many of the medical procedures we take for granted. Of particular concern is the rise in resistance within Gram-negative bacteria, as these organisms are highly transmissible and share resistance genes easily. We need to optimise the amount of antimicrobials we give patients to improve patient outcomes and reduce toxic side effects and the development of AMR. Antimicrobials are frequently prescribed according to a one size fits all model yet, responses to antimicrobials vary widely, particularly across clinical scenarios and certain patient groups e.g. in ITU, sepsis, surgical and obese patients. To overcome this, our research team have developed a small, painless biosensor technology that can monitor antimicrobial levels so that appropriate therapeutic levels can be given in real-time. This project aims to develop and evaluate the biosensor closed-loop technology for antimicrobials with activity against Gram-negative organisms using aptamer-based technologies and assess its utility as part of a clinical validation study. The yearly objectives are: Y 1-2. Develop the biosensor with different sensor technologies and assess the biosensor’s utility and acceptability in healthy volunteers using a range of antimicrobials. Y2-3. Evaluate the sensor in different patient groups and in different conditions including the obese and those in intensive care, and in Y3, develop algorithms that can automatically adjust doses to achieve optimal levels.
This studentship offers an exciting opportunity to work on innovative, cutting edge technologies to improve patient care and address the challenge of AMR. The student will benefit from the knowledge and expertise of the well established, multidisciplinary team, which includes our industrial pharmaceutical partner Shionogi, and members of Imperial College’s Departments of Medicine, Bioengineering and Chemistry.
Project title: High throughput and effective transfection of cells using innovative methods and materials
Lead supervisor: Professor Molly Stevens
Cell transfection is one of the most powerful techniques within cell therapy, regenerative medicine, cell biology and the life sciences, though there are several drawbacks such as safety concerns and low-throughput, respectively, limiting their range of applicability as well as clinical impact. Within this PhD studentship, we will use a combination of state-of-the-art material technologies available within Prof Molly Stevens’s labs (www.stevensgroup.org) and TTP plc, to design and optimise transfection assay protocols for cells such as cardiac cells and immune cells, available within Prof Sian Harding's research programme. Supervised by Profs Stevens and Harding, the student will be trained within a vibrant and multidisciplinary environment in state-of-the-art material designs and engineering, cell biology and nanotechnology. An ambitious and pro-active student will be given top training in these fields towards the goal of creating a high-throughput cell transfection system based on platform technologies available within Imperial College London and TTP plc.
Project title: Potential therapeutic effects of engineered Clostridium STp products on immune activity
Lead supervisor: Professor Stella Knight
The microbiota, which includes >1000 bacterial species in the intestine, has a profound effect on health. Abnormal immune responses to gut bacteria drive inflammatory bowel disease (IBD), a chronic inflammatory condition which has increased in incidence in the UK to around 300,000. Symptoms, including diarrhoea, cramps, pain, fatigue, weight loss and anaemia, are distressing and current treatments frequently fail. There is a need for novel disease-modifying treatments. The APRG laboratory at Imperial has discovered and patented a molecule called STp, derived from a probiotic bacterium present in the gut, and generated preliminary evidence that it can inhibit or prevent gut inflammation. CHAIN biotech are a new company that has developed a novel way of delivering therapeutic substances directly to the gut by engineering safe probiotic bacteria. This technology has the potential to result in efficient new treatments for a range of gut diseases. This project will be a collaboration between APRG and CHAIN, bringing together the immunological expertise of APRG academics with the technical and product development expertise of CHAIN biotech. The aim of the project is to test the potential therapeutic effects of STp produced by an engineered bacteria on gut immune activity. Proprietary test materials will be studied for their effect on immune cells (Year 1), their imprint on immunity in health vs disease (Year 2) and their therapeutic effects on inflammatory disease (Year 3). The student will gain knowledge of immunology, molecular biology, biotherapeutic product development and the potential of the microbiome to improve human health.
Project title: Identifying biomarkers of treatment response in gestational trophoblastic disease through quantitative proteomics analysis of patient samples
Lead supervisor: Dr Olivier Pardo
Gestational trophoblastic disease (GTD) is a spectrum of disorders including the pre-malignant hydatidiform mole (HM) through to malignant choriocarcinoma. Methotrexate (MTX)-based mono-chemotherapy, a low toxicity regimen, cures the vast majority of cases. A multi-parametric scoring system (FIGO) is used to predict patients with MTX resistance that require various more toxic combination therapies. However, this system misclassifies ≈30% of patients with innate MTX resistance, unnecessarily delaying commencement of combination agent chemotherapy. Whilst nearly all patients are ultimately cured, some still die from metastatic/multi-drug-resistant disease. We think these deaths can be eliminated by better stratification of patients to effective initial treatments and/or through development of novel therapeutic strategies. The student, following training in proteomics and bioinformatics at Gemini Biosciences, will perform quantitative proteomics analysis of MTX sensitive vs resistant vs multidrug sensitive vs resistant patient tissue samples to identify potential new biomarkers to ensure the most effective treatment is given to the right patient at the right time. This work should also reveal possible novel therapeutic targets. The biomarkers and possible therapeutic targets will be validated using our unique large GTD patient tissue collection with allied clinical data. Possible therapeutic targets will be further tested in our pre-clinical models of GTD using a broad range of cell and molecular biology techniques in vitro and in vivo. In summary, this PhD provides an outstanding opportunity for multidisciplinary training in a diverse research environment generating data that should change clinical practice and benefit GTD patient outcomes.
Project title: New age antibiotics: Bacteriocins
Lead supervisor: Professor Ramesh Wigneshweraraj
Antibiotic resistant bacterial infections place a significant burden on healthcare systems worldwide. As such, alternative and innovate approaches are needed to manage and treat bacterial infections. In this project, we will study the potential of bacteriocins – antibacterial toxins produced by bacteria - as a novel therapeutic option against antibiotic resistant clinical isolates of major bacterial pathogens. Bacteriocins affect diverse processes in the target bacteria. This project will specifically focus on bacteriocins that inhibit mRNA synthesis - transcription - in target bacteria. Therefore, the project we will also involve identifying bacteriocins that specifically inhibit the transcription machinery - the RNA polymerase - and determine the mechanism of their action at a molecular level. The student will be offered training is a diverse range of methods relevant to training the next generation of scientist in the space of antibacterial drug discovery and will involve bacteriology, biology of bacteriocins and RNA polymerase biochemistry. At the industrial partner site (Syngulon), the student will learn about the application of synthetic biology methods to synthesise bacteriocin in addition to numerous interdisciplinary skills based training related to innovation driven research, product development, data management, patent management.