Infection, Immunity, Antimicrobial Resistance & Repair Projects

The details of the available projects for the Infection, Immunity, Antimicrobial Resistance & Repair theme are outlined on this page. You can find other projects on the Neuroscience & Mental Health and Population Health Sciences pages. A full list of our available projects can be downloaded below.

GW4 BioMed2 MRC DTP – Full list of available projects 2022-23

For full project descriptions, including contact details for the lead supervisor, click the download link on the project title.

Applications to the GW4 BioMed2 MRC DTP will be accepted via this online survey until 5pm on 26th November 2021. For guidance on the application criteria and decision timeline, please see the information here.

Polyamine-based antimicrobials for treatment of antibiotic resistant bacterial pathogens.

Antimicrobial resistance (AMR) is one of the top 10 global health issues. Lack of novel drugs in the clinical pipeline are severely hampering treatment options and driving AMR. We have identified novel polyamine-based compounds displaying activity against major human bacterial pathogens. This project will further define the molecular activity of these compounds using a suite of chemical and molecular microbial methods together with invertebrate infection models.

Lead Supervisor: Dr Ian Blagbrough
Institution: Bath

Control of mucosal immunity and intestinal integrity by human gamma/delta T cells

γδ T cells are ‘unconventional’ lymphocytes that promote mucosal barrier defence and regulate immune responses to microbial infection. This PhD will use gene expression profiling, functional studies on cells from human blood and intestine, and organ chip-based / in vivo models to define how microbe-responsive γδ T cells control CD4+ T cell immunity and intestinal barrier function in health and inflammation.

Lead Supervisor: Prof Matthias Eberl
Institution: Cardiff

Escaping host immunity: Characterising immune evasion mechanisms employed by the bacterial pathogen Staphylococcus aureus

The complement system plays a major role in defence against infection. How major human pathogens such as Staphylococcus aureus resist this element of host immunity is currently unclear. By employing gold-standard phenotypic, transcriptomic and functional genomic techniques, this project will reveal important virulence factors and virulence gene regulatory networks that promote resistance to complement, offering new targets for future therapeutic intervention.

Lead Supervisor: Dr Maisem Laabei
Institution: Bath

The role of ‘parasitism islands’ in infection by soil-transmitted helminths

Soil-transmitted helminths (STH) infect 1.5 billion people globally and cause a substantial global health burden This project will investigate a novel concept in parasite biology: the physical organisation of important parasitism genes in genomic parasitism islands. In this project, we will investigate architecture, regulation and function of parasitism islands. Understanding the role of parasitism islands could lead to improved STH control and treatment strategies.

Lead Supervisor: Dr Hans-Wilhelm Nuetzmann
Institution: Bath

Attributing the source of antimicrobial resistant diarrheal pathogens in African children

Diarrhoeal disease is a major cause of mortality among children in low-income countries. Joining a large MRC funded program you will collect and sequence metagenome samples to quantify the relative contribution of different antimicrobial resistant pathogens to human infection. Time spent in Bath, Bristol and The Gambia will help understand transmission networks, and bioinformatics and machine learning risk models will identify effective interventions.

Lead Supervisor: Prof Samuel Sheppard
Institution: Bath

Multi-scale modelling of COVID-19 transmission, with application to new and on-going vaccination strategies

Mathematical models have played a central role in guiding interventions to control COVID-19. Existing models have not captured infection variability within an individual and the dependence on personal characteristics. Using within-host data to capture infection kinetics and surveillance data to capture epidemic dynamics, models will elucidate the role of immunity in long-term COVID control.

Lead Supervisor: Dr Ellen Brooks-Pollock
Institution: Bristol

Establishing Magnetic Nanoparticle Design Guidelines for Maximizing Clinical Efficacy

Using nanotechnology in medicine has been widely discussed for several decades yet remains elusive due to questions surrounding effectivity, biocompatibility and in vivo clearance. Supervised across Universities of Bristol, Bath and Cardiff, this interdisciplinary project will develop design guidelines for customizing biocompatible magnetic nanoparticles based on the target clinical application such as magnetic hyperthermia and site-specific drug delivery.

Lead Supervisor: Dr James Byrne
Institution: Bristol

Accelerated prediction of virulence and antibiotic susceptibility for bacteria causing bloodstream infections using MALDI clinical diagnostics

In time-critical infections it is crucial to deliver working antibiotics fast but testing for antibiotic resistance is slow. We have developed machine learning tools that help detect bacterial types associated with enhanced virulence and resistance from routine MALDI mass spectrometry data. You will develop this approach for clinically-important Klebsiella pneumoniae and Escherichia coli bacteria additionally performing gene knockout experiments and bioinformatics.

Lead Supervisor: Prof Andrew Dowsey
Institution: Bristol

Identifying new therapeutic targets and testing their potential for the treatment of chronic inflammation in arthritis

Drugs that block cytokine activity have revolutionised the treatment of rheumatoid arthritis. However, the ~40% of patients who develop ectopic lymphoid-like structures (ELS) within inflamed joints continue to display severe disease and an inadequate response to these current drugs. The PhD student will use in vivo arthritis models, imaging and cutting-edge next-generation sequencing methods to find new ways of targeting ELS to support precision medicine.

Lead Supervisor: Dr Gareth Jones
Institution: Bristol

Sticky but not sweet: deciphering how Streptococcus bacteria drive clot formation and heart disease

Streptococcus bacteria cause heart disease infective endocarditis (IE), for which novel therapies are urgently needed. Bacterial protein PadA is critical to IE pathogenesis but how it functions is unknown. This project combines molecular/clinical microbiology, host immunity and structural biology to identify the mechanisms by which PadA aids bacterial survival in blood and drives the harmful clot formation seen with IE. Such insight is critical to IE therapy design.

Lead Supervisor: Dr Angela Nobbs
Institution: Bristol

The spread of anti-microbial resistance plasmids in humans, animals and the environment.

Mitigating the global impact of antimicrobial resistance (AMR) requires targeted surveillance and intervention within different clinical, community, animal and environmental settings. This project will help to prioritise such approaches by examining how the adaptation of bacterial strains to different niches impacts on the spread of any AMR plasmids they carry. This interdisciplinary approach will involve bioinformatics, modelling and competition experiments.

Lead Supervisor: Professor Edward Feil
Institution: Bath

The regulation of tumour cell cytolysis by cancer associated fibroblasts

Cytotoxic T cells can kill tumour target cells. However, this ability is widely suppressed in the tumour microenvironment. Using the in vitro reconstruction of this environment with three-dimensional tissue cultures, you will investigate how tumour associated fibroblasts in various differentiation states regulate cytolytic tumour cell killing per se and, in collaboration with our industrial partner AstraZeneca, upon therapeutic intervention.

Lead Supervisor: Dr Ute Jungwirth
Institution: Bath

The path of least resistance: Genomics-driven antibiotic discovery from the bacterial resistome

Antimicrobial resistance is one of the greatest threats to global public health. One solution to this problem is to identify new antibiotics that are effective against resistant microbes. To achieve this ambition, this project will employ a novel genomics-led approach to identify new natural product-based antibiotics from deep-sea bacteria. This is an interdisciplinary project, which involves working collaboratively with groups in South Africa and in industry.

Lead Supervisor: Prof Paul Race
Institution: Bristol

Identifying the impact of genetic variants of MICB associated with severe and symptomatic dengue virus infection on NK and CD8+ T cell function

NK and CD8+ T cells are critical components of anti-viral immunity; they express NKG2D which modulates their functions through binding to the inducible MICB ligand. Polymorphisms in MICB associate with increased susceptibility to severe dengue virus infection. You will investigate the mechanistic basis for the association of MICB polymorphisms and severe dengue by using state-of-the-art immunological, genetic and bioinformatic methodologies and work in a Cat-3 lab.

Lead Supervisor: Dr Laura Rivino
Institution: Bristol

Primary cilia assembly, disassembly, and cell proliferation in the context of wound repair

Primary (non-motile) cilia are hair-like extensions present on almost all animal cells that act as antenna for extracellular signals. Recent data has identified a key role for ciliary signalling in healing wounds and bone fractures. Primary cilia could be attractive targets to intervene in fibrosis and scarring. We have ambitious plans to use in vitro biochemistry, high resolution microscopy, and phosphoprotoemics to explore this opportunity.

Lead Supervisor: Prof David Stephens
Institution: Bristol

Anticipating antimicrobial resistance: predicting the resistance-spectrum of emerging β-lactamase variants using atomistic simulation and experiment

Antibiotic resistance threatens human health. β-lactamases cause resistance to β-lactams, the most widely used antibiotics. Pathogenic bacteria frequently pick up newly evolved β-lactamases in their environment, leading to hard-to-combat bacterial infections. By using atomistic simulation and experiment, we can anticipate which new resistance patterns may arise and how. This will be an advantage in the ‘biochemical warfare’ between humans and bacteria.

Lead Supervisor: Dr Marc van der Kamp
Institution: Bristol

Equipping Antigen-Specific T Cells With the Ability to Remodel the Tumour Microenvironment to Improve Cancer Rejection

The anti-cancer T cell response can drive structural alterations to the tumour microenvironment (TME) which amplify the immune response promoting tumour destruction. This project will determine whether immunotherapy can be enhanced by empowering T cells with the ability to alter the TME, tipping the balance in favour successful T cell driven cancer therapy.

Lead Supervisor: Prof Awen Gallimore
Institution: Cardiff

Using synthetic biology to target agents of antimicrobial resistance

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.

Lead Supervisor: Dr Dafydd Jones
Institution: Cardiff

Suppression of T cell immunity and antibody production during virus infection and sepsis

The generation of protective antibodies against infection is dependent on “help” from CD4+ T follicular helper (TFH) cells which are elicited in response to bacteria and viruses, such as influenza and SARS CoV-2. However, these cells can decline when immune responses are over-exaggerated (sepsis). The student will use immunological techniques and innovative gene profiling strategies to examine why low numbers of CD4+ TFH cells correlate with poor outcome in sepsis.

Lead Supervisor: Dr James McLaren
Institution: Cardiff

Epigenetic regulation of microglial gene expression in Alzheimer’s disease

Neuroinflammation is a prominent event Alzheimer’s disease (AD) pathogenesis, driven by activation of microglia, the brains resident immune cells. To define how microglial gene expression is regulated in AD, this project utilises a state-of-the-art human stem cell culture model of AD coupled with epigenomic profiling and bioinformatic analysis. The role of prioritised genes will then be described through functional assays of important microglial processes.

Lead Supervisor: Dr Owen Peters
Institution: Cardiff

Development of HLA-agnostic broad-spectrum cancer immunotherapies

T-cell therapies are the biggest development in cancer treatment in over 50 years with some forms now given on the NHS. We work closely with industry to develop new immunotherapies for cancer. We have a bank of T-cell receptors (TCRs) that see most cancers from all people via several new ligands (e.g. Nat Immunol 21, 178). This project will characterise some of these “HLA agnostic” TCRs with a view to developing next generation TCR-T therapies for cancer.

Lead Supervisor: Prof Andrew Sewell
Institution: Cardiff

Investigating the mechanisms, and immunological consequences, of viral cell-cell spread

Viruses can infect as cell free virus, or transmit directly from cell-to-cell. Cell-cell spread dramatically alters susceptibility to the immune system and therapeutics, yet we have very little understanding of this process. We will use molecular virology, proteomics, and cutting-edge imaging, to work out how cell-cell spread occurs, how it enables viruses to escape immunological and therapeutic control, and how therapeutics might be overcome this problem.

Lead Supervisor: Dr Richard Stanton
Institution: Cardiff

Generating killer cells for immunotherapy against cancer and pathogen

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. This knowledge will aid the development of immunotherapies using such effector cell types to target many different diseases. We will use human cytomegalovirus and leukaemic cells as systems of analysis.

Lead Supervisor: Dr Eddie Wang
Institution: Cardiff

Deadly fungus in the brain: Impact of infection on immunometabolic responses in glia

Fungi cause deadly brain infections in humans; to better combat these deadly invaders and prevent brain damage. we must understand brain-specific immune responses during infections. To achieve this, the student will use key models of infection, including mouse and zebrafish, coupled with state-of-the-art tools in live quantitative microscopy, metabolism and immunology to uncover the mchanisms which determine the outcome of this deadly disease.

Lead Supervisor: Dr Carolina Coelho
Institution: Exeter

Genome evolution and epidemiology of hospital-acquired Candida infections in the UK

Fungal diseases kill more than 1.5 million people every year, and cause disease in over a billion people. One of the most important fungal pathogens of humans worldwide is Candida albicans. We use genomic epidemiology to understand its evolution and the genes that drive its pathogenicity. The project will use both dry-lab and wet-lab approaches to make fundamental discoveries in medical mycology.

Lead Supervisor: Dr Rhys Farrer
Institution: Exeter

Novel phage-inspired antibiotic therapies

Antimicrobial resistance is one of the most pressing public health challenges and threatens the ability to effectively fight infectious diseases, with around 10 million people predicted to die annually of infections by 2050. This project will tackle antimicrobial resistance by studying how bacteriophages and antibiotics can synergise to kill bacterial pathogens. This novel knowledge will be paramount for the development of new antimicrobial therapies.

Lead Supervisor: Dr Stefano Pagliara
Institution: Exeter

The filamentous growth of fungal killers: a combined mathematics and lab approach

In this PhD, you will use mathematics, computer programming and lab-based experiments to investigate the invasive growth of the two major filamentous human pathogens – Candida albicans and Aspergillus fumigatus. The findings will have important implications for understanding tissue invasion during life-threatening fungal infections. Unlike most PhDs, this is an excellent opportunity to be trained in both the experimental and mathematical aspects of modern research.

Lead Supervisor: Dr David Richards
Institution: Exeter

Developing a national capacity for adjunctive phage therapy to treat antibiotic-resistant respiratory infections through Citizen Science

Phage therapy promises the next generation of targeted antimicrobials to answer the threat of antimicrobial resistance. Phages are predators of bacteria which can be isolated from the environment and combined with antibiotics to re-sensitise resistant bacteria. The student will use high-throughput liquid handling and citizen science to isolate phages targeting pathogens associated with respiratory disease and develop a Citizen Phage Library for novel therapeutics.

Lead Supervisor: Dr Ben Temperton
Institution: Exeter

Developing new technologies to target AMR

Antimicrobial resistance (AMR) has been described as a slow-motion pandemic that already has a huge impact on healthcare, and will become much more problematic in the next decades if the tide is not turned. Finding new ways to eradicate AMR could be a real game changer. This project will explore CRISPR-Cas9 in combination with lytic bacteriophage as a new antimicrobial tool to target drug resistant bacteria in the gut microbiome.

Lead Supervisor: Dr Stineke van Houte
Institution: Exeter

Emerging Aspergillus infections: tackling fungal adaptation

Fungal infections caused by Aspergillus species are a serious threat to immunocompromised patients and those with chronic lung disorders and influenza or SARS-CoV-2 induced pneumonia. Moreover, resistance to antifungals and host defences are emerging and increasing the case-fatality rate. Deploying cutting-edge 3D chromatin genetics, we aim to unravel how changes in chromosome architecture underpins fungal adaptation and to find new ways to tackle fungal infections.

Lead Supervisor: Prof Adilia Warris
Institution: Exeter

Mathematical Modelling for the Prediction of Aerobic Fitness in Paediatric Patients with Cystic Fibrosis

A core goal for treating cystic fibrosis is to improve patients’ aerobic fitness, which incorporates function of the cardiovascular, pulmonary and muscular systems. Despite knowledge of these systems in isolation, little is understood about the complex interactions between them. This project aims to construct and analyse dynamic, multi-organ mathematical models to elucidate to assess how the quantitative relationships between these systems impact aerobic fitness.

Lead Supervisor: Dr Kyle Wedgwood
Institution: Exeter

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