Infection, Immunity and Repair Projects

Applications for studentships for our 2019/20 intake have now closed. The below information refers to the 2019/20 recruitment round. 

Please find the details of the available projects for the Infection, Immunity and Repair theme outlined below. A full list of our available projects can be downloaded here.
Full project descriptions, including contact details for the lead supervisor, can be downloaded by clicking on the link in the project title.

Understanding prostate cancer prognosis and disease progression: interplay between lifestyle, anti-cancer immune competency, metabolism, and genetics

The effectiveness of prostate cancer therapy varies between patients. This highly interdisciplinary project will examine whether lifestyle factors such as exercise predict prostate cancer outcomes. Specifically, the project will assess the interplay between exercise, immunity, metabolomics and genetics in men with prostate cancer.

Lead Supervisor: Dr John Campbell.
Institution: Bath.

Computational modelling for prevention of heart failure following myocardial infarction

This project will develop a state-of-the-art computational model of cardiac perfusion and tissue remodelling following a myocardial infarction, using data acquired by PET/CT imaging of a novel mouse experimental protocol. The model will form a key part of an in silico tool for developing the next generation of therapies for heart failure.

Lead Supervisor: Dr Andrew Cookson.
Institution: Bath.

Targeting a novel allosteric site on Trypanosoma cruzi trans-sialidase for future Chagas’ disease therapy

Chagas’ Disease, caused by T. cruzi, lacks effective treatment and results in major morbidity in Latin America. A newly-identified allosteric site on a surface enzyme may be a breakthrough. Inhibitor synthesis will be combined with laboratory characterisation, protein structure and computer simulation to target this neglected tropical disease.

Lead Supervisor: Dr Susan Crennell.
Institution: Bath.

Development of a multiplex sensing platform for accurate and rapid diagnosis of sepsis

Sepsis kills one person every few seconds. Clinical symptoms and current laboratory diagnostics do not allow definitive early diagnosis. This collaborative project aims to address this shortcoming through the development of a novel sensing platform, capable of detecting both pathogen associated and host immune markers of sepsis at point-of-care.

Lead Supervisor: Dr Pedro Estrela.
Institution: Bath.

Defining the role of efflux in Proteus mirabilis biofilm formation and catheter associated urinary tract infection

Biofilms are a major cause of antimicrobial resistance (AMR) and undermine treatment of infections. Working with Public Health England, the student will employ genetic, transcriptomic, and infection-modelling techniques to understand the role of efflux systems in biofilm formation. This will support the development of new anti-biofilm agents.

Lead Supervisor: Dr Brian Jones.
Institution: Bath.

Ligament repair strain sensors: improving monitoring after ligament reconstruction surgery

Investigation of a novel polyethylene suture with radiopaque (X-ray visible) marks along its length, intended for direct measurement of strain after suture augmented ligament repair using X-ray imaging methods. The project would be experimental, focused on materials and imaging, but also involve collaboration with orthopaedic surgeons and industry.

Lead Supervisor: Dr Elise Pegg.
Institution: Bath.

A new technological platform for personalised cell therapy

Advanced cell-based therapeutics will shift toward personalised solutions where patients are treated as individuals rather than receiving one-size-fits all treatment. To enable this, we propose a highly interdisciplinary project that will lead to an innovative real-time monitoring and control platform for automated stem cell culturing.

Lead Supervisor: Dr Mirella Di Lorenzo.
Institution: Bath.

What characterises an effective immune response to group A streptococcal throat infection?

The project will describe immune responses to Group A streptococcal (GAS) pharyngitis in children. Quantitative sequencing of T-cell receptors will be established in healthy (GAS-immune) adults and applied to acute & convalescent blood from throat swab GAS-positive children and negative controls. The results will inform the design of GAS vaccines.

Lead Supervisor: Professor Adam Finn.
Institution: Bristol.

Expression and characterization of human autoantibodies from single B cells in type 1 diabetes

B cells play a key role in type 1 diabetes (T1D). Using the latest advances in single cell analysis, human B cells from pancreas, lymph node or skin samples of patients with T1D will be isolated, their transcriptome analysed and their immunoglobulin heavy and light chains expressed to allowed autoantibody analysis at the monoclonal level.

Lead Supervisor: Dr Kathleen Gillespie.
Institution: Bristol.

Using zebrafish to probe the role of the immune system in skeletal regeneration throughout life

10.8 million people in the UK have a chronic skeletal condition; age is a major risk factor. Using live imaging we will test how the cells of the skeletal and immune systems interact in young, mature and aged zebrafish. Using mutants that age prematurely we will test whether manipulation of key signalling pathways can restore regenerative capacity.

Lead Supervisor: Dr Chrissy Hammond.
Institution: Bristol.

Modelling the cell biology of wound healing in flies and in silico

This project will utilise live in vivo imaging in translucent fruitflies combined with cutting-edge biophysical mathematical modelling, to investigate how epithelial tissues heal wounds and how events might be modulated to improve healing. For translational relevance, these studies will integrate with clinical studies using patient wound samples.

Lead Supervisor: Professor Paul Martin.
Institution: Bristol.

Characterisation of a membrane protein critical to Staphylococcus aureus pathogenicity and immune escape

Staphylococcus aureus is a major human pathogen. We have recently discovered that S. aureus membrane protein MasA facilitates expression of toxins that exacerbate disease and protects the bacterium from immune attack. This PhD will characterise this dual MasA function with a view to developing novel therapeutic approaches.

Lead Supervisor: Dr Ruth Massey.
Institution: Bristol.

The role of IL-27R in the regulation of retinal diseases

Cytokines play a crucial role in controlling inflammation. The cytokine IL-27 interacts with immune cells and with retinal photoreceptors to protect the eye from damage. This project will use mice deficient in IL-27 signalling to investigate the cytokine’s role in acute autoimmune inflammation (uveitis) and choroidal neovascularisation.

Lead Supervisor: Dr Lindsay Nicholson.
Institution: Bristol.

Roles of Eph tyrosine kinases in T-cell responses to melanoma

Cancer growth is kept under control by immune cells such as T-cells. New T-cell-based immunotherapies successfully eliminate melanoma in some patients, but the majority of patients show no response. This project aims to determine whether Eph receptor tyrosine kinases enhance T-cell recruitment to melanoma, which could improve patient outcome.

Lead Supervisor: Professor Anne Ridley.
Institution: Bristol.

Countering antimicrobial resistance: investigating β-lactamase inhibitors using atomistic simulation and experiment

Antibiotic resistance threatens human health. β-lactamases give resistance to β-lactam antibiotics. Some can be countered with inhibitors, which may also halt bacterial growth. We will investigate these differences by simulation and experiment, develop simulation protocols to predict inhibitor activity, and use these to guide inhibitor design.

Lead Supervisor: Dr Marc van der Kamp.
Institution: Bristol.

Uncovering novel genetic pathways that promote tissue repair and healthy ageing, using live-imaging and functional analyses within in vivo animal models and human genetic epidemiology

This multidisciplinary project integrates live-imaging and genetics in Drosophila with cutting-edge human genetic epidemiology, to explore the diverse repair mechanisms used by developing and physiologically-active body tissues to resist or recover from ‘stress’ (metabolic, inflammatory and environmental) and explore their links to human disease.

Lead Supervisor: Dr Helen Weavers.
Institution: Bristol.

A biosensor for the rapid detection of antibiotic resistant tuberculosis in nomadic African populations

Tuberculosis infects one third of the worlds population. This project will advance the development of a real time (15 min), portable, low cost, simple to use assay capable of diagnosing the disease in remote locations in Africa. This is a unique opportunity to work with engineers, biologists and clinicians to reduce human suffering.

Lead Supervisor: Professor Les Baillie.
Institution: Cardiff.

Control of adaptive immunity in health and inflammation by human blood and mucosal gamma/delta T cells

γδ T-cells are ‘unconventional’ lymphocytes that regulate immune responses to infection and promote mucosal protection. The PhD student will use gene expression profiling and functional studies using cells from human blood and intestine and in vivo models to define how microbe-responsive γδ T-cells control CD4+ T-cells in health and inflammation.

Lead Supervisor: Prof Matthias Eberl.
Institution: Cardiff.

Targeting LAG3+ T cells for Cancer Immunotherapy

Some malignancies can be controlled by immunotherapy, but most colorectal cancers (CRC) remain unresponsive. We have evidence that the immune checkpoint, LAG3, is important in CRC. Using in vivo models and patient derived organoids, the hypothesis that removing LAG3+ T cells will unleash effective anti-CRC immune responses will be tested.

Lead Supervisor: Professor Andrew Godkin.
Institution: Cardiff.

Characterising the interaction of coagulation and innate immunity in people being treated for bleeding disorder haemophilia A

A novel treatment for haemophilia patients has been associated with thrombosis in small blood vessels in the kidney. This is also found in a rare kidney disorder caused by impaired immune function of blood proteins. This project will determine the mechanisms of this treatment on coagulation and immune system by in vitro tests and clinical samples.

Lead Supervisor: Dr Meike Heurich.
Institution: Cardiff.

Enhancing immune stimulation for novel anti-cancer viral vaccine vectors

HCMV is one of the most promising vaccine vectors for inducing T-cell responses against pathogens and cancer. However it’s unclear how these responses are induced. We will combine cutting-edge proteomics with molecular virology and immunology to determine how HCMV induces such strong responses, enabling us to generate optimised vaccine vectors.

Lead Supervisor: Dr Richard Stanton.
Institution: Cardiff.

Flexible vectors for immunotherapy against cancer and pathogens

Natural killer cells (NK) and CD8+ T cells protect us against intracellular pathogens and cancers. This project aims to determine pathways that can drive the growth of particular types of NK and T cells that are optimised to provide better protection from disease. We will use cytomegalovirus and leukaemic cells as systems of analysis.

Lead Supervisor: Dr Eddie Wang.
Institution: Cardiff.

Bacteria-phage interactions during clinical phage therapy

With the rapid increase antibiotic resistance, alternative antimicrobials are desperately needed. Viruses that kill bacteria (phages) may be useful, but we know little about how these organisms interact during treatment. The project will involve population and genomic analysis of bacteria and phages from patients that have undergone phage therapy.

Lead Supervisor: Professor Angus Buckling.
Institution: Exeter.

Improving diagnosis of adult onset Type 1 diabetes using islet autoantibodies

Misdiagnosis of adult Type 1 diabetes is common, leading to poor treatment. Current available laboratory tests do not allow definitive diagnosis. This clinical research project will improve islet autoantibody testing and inform the best way to use these tests in the NHS, to help patients with Type 1 diabetes get the right diagnosis and treatment.

Lead Supervisor: Dr Angus Jones.
Institution: Exeter.

Old red blood cells and the immune system: phagocytosis, membrane stiffness and “eat-me” signals

This PhD will investigate, using a combination of experiments and simulations, how old red blood cells are cleared by our immune systems. This has implications for a variety of conditions such as sickle-cell anaemia and thrombosis. Unlike most PhDs, this is a unique opportunity to learn both the modelling and experimental sides of modern research.

Lead Supervisor: Dr David Richards.
Institution: Exeter.

Quantitative description of protein interactions in the Wnt signalling network in vivo

Wnt signalling regulates a broad variety of processes during embryonic development and disease. In vertebrates, Wnt proteins are distributed along signalling filopodia – called cytonemes – between cells. The aim of this project is to quantitatively describe Wnt ligand-receptor interactions at cytoneme contact points in vivo.

Lead Supervisor: Professor Steffen Scholpp.
Institution: Exeter.

Modifying protein clustering as a novel repair strategy in heart failure

Heart failure currently lacks effective therapies to restore heart function. We will evaluate a new approach to boost heart cell function by modulating the molecular clustering of receptors critical for forceful contraction. We will combine quantitative super-resolution microscopy and stem cell technology to address this important health problem.

Lead Supervisor: Professor Christian Soeller.
Institution: Exeter.

Treating diabetic inflammation using AMP-activated protein kinase activators: Working with industry

Inflammation is common in diabetes and contributes to disease by increasing risk for heart attacks and strokes. In this project, the student will use novel drugs targeting the AMP-activated protein kinase (AMPK) pathway. We will work with Rigel Pharmaceuticals, Inc., to determine whether drugs targeting AMPK reduce inflammation caused by diabetes.

Lead Supervisor: Dr Craig Beall.
Institution: Exeter.


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