Infection, Immunity and Repair Projects

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 can be downloaded by clicking on the link in the project title. Contact details for the lead supervisor can be found by clicking on their name.

For details on how to apply, please head back to our How to Apply page. Our application form can be found here.

 

Dissecting an antibiotic resistance network in the hospital ‘superbug’ Enterococcus faecalis
Enterococcal infections are a major public health burden and often due to a striking degree of drug resistance. This project will apply genetics, biochemistry and modelling to gain a better understanding of the molecular mechanisms and systems level organisation of resistance. Ultimately, this is aimed at identifying potential new drug targets.
Supervisor: Dr Susanne Gebhard.
Lead 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.
Supervisor: Dr Pedro Estrela.
Lead Institution: Bath.

Computational modelling for prevention of heart failure following myocardial infarction
The challenge is to develop a validated computational model of perfusion and tissue remodelling in the mouse heart for healthy and diseased states using data currently being acquired from PET/CT imaging and experiments. This model will form a key part of an in silico tool for developing the next generation of therapies for cardiovascular diseases.
Supervisor: Dr Andrew Cookson.
Lead Institution: Bath.

Blood-borne microparticles: Enigmatic cell-derived vesicles with a causal role in skin and lung fibrotic diseases?
This multi-disciplinary, cross-institutional studentship will use cutting-edge technologies including nanoparticle tracking analysis, proteomics and transcriptomics (plus bioinformatic analysis) to evaluate the source, content and contribution of circulating microparticles in the development of two life-threatening fibrosing diseases.
Supervisor: Dr John Pauling.
Lead Institution: Bath.

DARPin-based biosensors for high-performance Tuberculosis Lab-on-Chip Point-of-Care diagnostic microsystems
Each year Tuberculosis kills 1.8 million people, mainly in developing countries. One major step forward is the development accurate Point-of-Care tests, with Lab-on-Chip technology being a key enabler. This cross-disciplinary project aims to develop such a novel diagnostic platform, exploiting the advantages of DARPins as biosensor binders.
Supervisor: Dr Despina Moschou.
Lead Institution: Bath.

Early detection of autoimmune disease by sensing autoantibodies directed against the autoantigenic post-translationome
We propose to develop an array-based electrochemical sensor for detection of multiple autoantibodies against post-translationally modified autoantigens. The sensor will comprise an array of modified autoantigens on a surface such as gold or graphene. Such a sensor will allow faster and earlier diagnosis of multiple autoimmune diseases.
Supervisor: Dr Stefan Bagby.
Lead Institution: Bath.

Understanding and addressing challenges in antibody labelling by new cross-disciplinary techniques for immunoPET imaging and sensing
A new synthetic methodology compatible with computational models of perfusion and tissue modelling in healthy vs. diseased states in hypoxia and normoxia will be developed. PET/CT imaging will be integrated with computational models forming a tool-kit for developing the next generation of diagnostics and therapies for non-communicable diseases.
Supervisor: Professor Pascu Sofia.
Lead Institution: Bath.

Anti-cancer immunity, liquid biopsies and lifestyle factors as predictors of breast cancer treatment outcomes
The effectiveness of breast cancer neoadjuvant chemotherapy varies between patients. This unique interdisciplinary project will examine whether anti-cancer immunity, circulating cell-free tumour DNA – a liquid biopsy – and variability in lifestyle factors known to influence immune function, predict breast cancer treatment outcomes.
Supervisor: Dr James Turner.
Lead Institution: Bath.

Modelling structure and interactions of antibodies and antigens
Knowledge of antibody structure is vital for medicine and biotechnology. Fast, accurate protocols incorporating flexibility and antibody-antigen binding will be developed and validated against structures from experiment. Modelling is aided for antibodies by division into highly variable antigen binding loops and a relatively invariant scaffold.
Supervisor: Professor Alison Walker.
Lead Institution: Bath.

Standardisation of microvascular imaging for unbiased assessment of reparative angiogenesis
Microvascular disease (MVD) urgently calls for new imaging and therapeutic approaches. We will test a modRNA therapy to help recovery from ischaemia and assess therapeutic results by unbiased analysis of microCT/PET imaging data. This multidisciplinary project will offer new means for effective diagnosis and therapy of MVD.
Supervisor: Professor Paolo Madeddu.
Lead Institution: Bristol.

Exploring the mechanism by which hyperactive platelets promote platelet-leukocyte interactions, innate immunity and deep vein thrombosis
Leucocytes are key players in causing deep vein thrombosis (DVT), a leading cause of cardiovascular death. This project will study the underlying mechanism by which hyperactive platelets activate the innate immune system and thereby contribute to DVT. Techniques include imaging, lipodomics, computational analysis and in vivo mouse models.
Supervisor: Dr Ingeborg Hers.
Lead Institution: Bristol.

Investigating the impact of inflammation after cancer surgery and radiotherapy in zebrafish and man
This project will utilise live imaging studies in translucent zebrafish to investigate how cancer biopsy/surgery and radiotherapy impact on the local innate and adaptive immune response and how this alters cancer progression for various cancer types.  The work will lead onto clinical studies using patient samples.
Supervisor: Professor Paul Martin.
Lead Institution: Bristol.

Live imaging and functional analyses of cardiac extracellular vesicles in zebrafish models of cardiovascular injury and repair
Membrane bound extracellular vesicles (EVs) carrying cargos (e.g. microRNAs) are released by cells as a form of intercellular communication. EVs have potential cardiovascular regenerative medicine applications, but there is insufficient understanding of endogenous EV function. This project will develop zebrafish models to study cardiac EVs in vivo.
Supervisor: Dr Rebecca Richardson.
Lead Institution: Bristol.

Application of stretchable electronics technology to research on bladder function
Loss of bladder control is a common and debilitating condition. This project will use state-of-the art stretchable electronics technology to develop sensors  to measure stretch of  the urinary bladder wall, to test their functionality  in vivo in animal models and apply the technology to investigate mechanism uncorking bladder malfunction.
Supervisor: Professor Christopher Fry.
Lead Institution: Bristol.

Understanding the translational requirements of stem cell differentiation
Understanding how stem cells can give rise to differentiating daughters that are different from themselves is poorly understood but is essential if we are to harness their power for regenerative therapies. This project will seek to determine how stem cell daughters change their translational programme as they leave the niche and differentiate.
Supervisor: Dr Marc Amoyel.
Lead Institution: Bristol.

Developing small molecule activators of the microtubule motor kinesin-1 for the manipulation of microtubule and organelle dynamics
You will seek to identify and develop small molecules that manipulate microtubule dynamics and organelle transport and begin to determine whether they may lead to the development of new research tools and new therapeutic strategies for treatment of cancer and neurological disease.
Supervisor: Dr Mark Dodding.
Lead Institution: Bristol.

Combining Computation and Experiment to study Resistance to Carbapenem Antibiotics
Carbapenems are among the most important antibiotics; OXA beta-lactamases cause resistance in a range of bacteria. This proposal combines computational chemistry, biochemistry and microbiology to investigate how OXA enzymes hydrolyse carbapenems and how sequence variation affects their activity, and identify candidate small molecule inhibitors.
Supervisor: Dr James Spencer.
Lead Institution: Bristol.

Control of CD4+ T cell responses by human 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.
Supervisor: Dr Matthias Eberl.
Lead Institution: Cardiff.

Dissecting the impact of L-selectin proteolysis on T lymphocyte dependent virus immunity
Killer T cells enter infected tissues to kill virus.  T cell entry into infected tissues requires the homing molecule L-selectin.  When killer T cells see virus they digest L-selectin and release fragments into the cell. This project will determine how fragments of digested L-selectin control the ability of killer T cells to detect and kill virus.
Supervisor: Dr Ann Ager.
Lead Institution: Cardiff.

Optimising expansion of CD8+ T cells for immunotherapy
CD8+ T cells protect against intracellular pathogens and cancers. Their use in immunotherapy, however, has been hampered as growing them in vitro leads to ‘exhaustion’ and ‘senescence’ impairing their survival. This project aims to determine new pathways that control their growth using cytomegalovirus and leukaemic cells as systems of analysis.
Supervisor: Dr Eddie Wang.
Lead Institution: Cardiff.

New approaches antimicrobial resistance detection and treatment
Your PhD project will look at new approaches that use engineered proteins as novel detection and treatment methods to tackle the growing treat of microbial resistance to commonly used antibiotics. You will target beta-lactamase enzymes, which are responsible for resistance to the most commonly used antibiotics, the penicillins.
Supervisor: Dr Dafydd Jones.
Lead Institution: Cardiff.

Using next generation approaches to define epidemiology and develop therapies for the neglected cystic fibrosis lung pathogen Burkholderia multivorans
Burkholderia multivorans is a transmissible and problematic cystic fibrosis (CF) lung pathogen. Despite now being most common Burkholderia in CF, it has been one of the least studied. Working with CF experts and industry, the student will undergo cross-disciplinary training in genomics, virulence modelling and novel therapy development.
Supervisor: Professor Eshwar Mahenthiralingam.
Lead Institution: Cardiff.

A Drosophila in vivo platform for the study of chronic radiation injury
Radiotherapy (RT) is an essential component of cancer treatment. Its efficacy is greatly limited by the chronic side effects of radiation injury, which can be severe and are difficult to predict. The project aims at developing model of chronic radiation toxicity using the Drosophila intestine, to dissect the genetic basis of RT late side effects.

Supervisor: Dr Joaquín de Navascués Melero.
Lead Institution: Cardiff.

Validation of a stem cell derived cartilage model for osteoarthritis research and drug screening
We have designed a method to produce tissue closely resembling articular cartilage from human stem cells. Novel biophysical techniques will confirm similarities in matrix architecture and cellular differentiation, enabling its use in research on osteoarthritis development, identification of disease biomarkers and screening of therapeutic agents.
Supervisor: Dr Sharon Dewitt.
Lead Institution: Cardiff.

Mechanisms controlling the switch between the pro- and anti-fibrotic functions of the long non-coding natural anti-sense to hyaluronan synthase 2
20% of the UK population has renal fibrosis and no interventions prevent/reverse its relentless fatal pathology.  This project uses state of the art molecular, biochemical and imaging techniques to investigate mechanisms underlying a newly-discovered long non-coding RNAswitch that controls whether cells take on a fibrotic or non-fibrotic phenotype.
Supervisor: Dr Robert Steadman.
Lead Institution: Cardiff.

Understanding how C-type lectin-like receptors collaborate to clear fungal infections
Antimicrobial resistance is a major problem and invasive fungal infections kill more people than TB or malaria. Various C-type lectin-like receptors are involved in anti-fungal immune responses. We will use novel genetic models and in vivo experiments to identify receptor collaboration and the therapeutic potential of targeting these receptors.
Supervisor: Dr Selinda Orr.
Lead Institution: Cardiff.

Gram-scale Production of Antibacterial Cyclic Peptide via a Synthetic Biology Approach
Antibacterial cyclic peptides are known for their high stabilities and can be used as anti-microbials for treating gastrointestinal infections, including ones caused by multi-drug resistant pathogens. This project will use an interdisciplinary approach to make cyclic peptides libraries at large scales and screen for their antibacterial properties.
Supervisor: Dr Louis Luk.
Lead Institution: Cardiff.

Advanced Virotherapies for Immuno-Oncolytic Applications
This project will develop refined virotherapies for the delivery immunotherapies in vivo. Cross cutting methodologies spanning molecular, proteomic, structural and immunological studies will be employed to better define how viruses infect cells, interact with host proteins and can be refined to mediate optimised delivery of immunotherapies to tumours.
Supervisor: Dr Alan Parker.
Lead Institution: Cardiff.

Extracellular trafficking of Wnt signal in gastric cancer
In this interdisciplinary PhD project, the student will develop new understanding of Wnt signal transport in gastric cancer. By combining the elegant tumour organoid culture system and zebrafish models, the student will investigate the mechanisms modulating production, spread and activity of this important signal in healthy and diseased tissue.
Supervisor: Dr Steffen Scholpp.
Lead Institution: Exeter.

Combatting antibiotic resistant pathogens by targeting the sensory networks controlling their virulence
Antibiotic resistance is a major problem in the treatment of bacterial infections. Novel ways of tackling infection are urgently needed. Bacteria rely upon sensory networks to sense threats and to respond accordingly. This project will target the sensory networks that bacteria depend upon for their virulence and their survival.
Supervisor: Dr Steven Porter.
Lead Institution: Exeter.

When red blood cell clearance goes wrong: the role of phagocytosis, membrane stiffness and “age-signalling” proteins
This project will investigate red blood cell clearance by the immune system. You will use a combination of mathematical modelling and lab work to dissect how membrane stiffness and “age-signalling” proteins affect red blood cell phagocytosis. This will allow you to develop computational, experimental, mathematical and image analysis skills.
Supervisor: Dr David Richards.
Lead Institution: Exeter.

Exosome characterization in immunity and development
Exosomes are showing increasing promise as canonical and epigenetic cell-cell communication shuttles. They are micro-vesicles that can package proteins and non-coding RNA cargo. This proposal will characterise exosomes in immune and developmental epigenetic signalling and their effect on cellular function in healthy and pathological conditions.
Supervisor: Dr Richard Chahwan.
Lead Institution: Exeter.

Using phage therapy to combat antibiotics resistant Pseudomonas aeruginosa infections
Pseudomonas aeruginosa is an opportunistic human pathogen causing infections in immunocompromised patients. Due to antibiotics resistance, phage therapy emerges as a promising treatment. This project examines how P. aeruginosa phage resistance depends on presence of other pathogens and its long-term consequences for P. aeruginosa virulence.
Supervisor: Dr Edze Westra.
Lead Institution: Exeter.

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