Applications for our 2020/2021 recruitment round are open from 29th September 2019 until 5pm on Monday 25th November 2019.
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 below.
Full project descriptions, including contact details for the lead supervisor, can be downloaded by clicking on the link in the project title.
Students can apply to the GW4 BioMed MRC DTP via this online survey by 5pm on 25th November 2019.
Antimicrobial resistance (AMR) can spread through microbial communities via parasites that jump between species, creating complex network of interactions. As such, controlling AMR will benefit from approaches developed for understanding ecological communities and social networks. The project will combine theory and laboratory techniques to do this.
Lead Supervisor: Professor Angus Buckling.
One in two people will be diagnosed with cancer during their lifetime. Positron Emission Tomography imaging is of paramount importance in clinical oncology. This project will develop Artificial intelligence (AI) solutions via deep learning to assist in the detection of cancer. Human in the loop technology such as eye tracking will be used to provide feedback to AI agents to expedite speed and accuracy of diagnosis by radiologist who interpret these images.
Lead Supervisor: Dr Rhodri Smith.
Neutrophils are abundant immune cells that are essential for defense against bacteria but little is known about their role in viral infections. The project will use advanced microscopy, flow cytometry and CRISPR gene editing to determine the molecular pathways controlling in vitro and in vivo neutrophil responses to two clinically relevant viruses: influenza virus and cytomegalovirus.
Lead Supervisor: Dr Borko Amulic.
Group A Streptococcus (GAS) causes a wide range of human diseases, but there is no vaccine available. Using tonsillar tissue and blood from children with GAS throat infections, this project will study immune responses to GAS and determine which vaccine antigens elicit protective responses.
Lead Supervisor: Professor Adam Finn.
Group B Streptococcus (GBS) is a major cause of severe neonatal disease. Maternal colonisation is the main transmission route. Using a range of genetic and biochemical approaches, this project will define the molecular basis of GBS colonisation through interactions with vaginal epithelium and Candida albicans. This will inform design of strategies to combat GBS disease.
Lead Supervisor: Dr Angela Nobbs
This project will create a state-of-the-art in silico tool to help develop the next generation of therapies for heart failure. Mathematical and computational models of cardiac tissue blood flow and the tissue remodelling that occurs following a heart attack will be created using data acquired by PET/CT imaging of a novel mouse experimental protocol. These models will then be used to predict the efficacy of new treatments for heart failure.
Lead Supervisor: Dr Andrew Cookson.
γδ T cells are ‘unconventional’ lymphocytes that regulate immune responses to infection and promote mucosal protection. This PhD will use gene expression profiling, functional studies on cells from human blood and intestine, and in vivo models to define how microbe-responsive γδ T cells control CD4+ T cell immunity in health and inflammation.
Lead Supervisor: Professor Matthias Eberl.
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.
Efflux systems are molecular “pumps” involved in many aspects of bacterial infection. Working with Public Health England, the student will employ genetic, transcriptomic, and modelling techniques to understand the role of efflux in biofilm formation and antimicrobial resistance. This will support the development of new ways to control infections.
Lead Supervisor: Dr Brian Jones.
A multidisciplinary PhD project, in which we will A) develop a cancer-on-a-chip microfluidic device and B) use the chip together with 2D & 3D co-cultures to study how insulin-like growth factor binding protein (IGFBP)-6 expression has an impact breast cancer progression and immune cell infiltration. Further, we will study IGFBP6 secretion into the blood of breast cancer patients prior to and after chemotherapy treatment.
Lead Supervisor: Dr Ute Jungwirth.
Personalised medicine is used to precisely diagnose patients and provide tailored treatment regimes. The presence of hypoxia in tumours requires specialized treatment, but is often difficult to identify. This project examines the synthesis of radiolabeled analogues of EF5, a hypoxia specific material, and its utility in diagnosing tumour hypoxia.
Lead Supervisor: Dr Matthew Tredwell.
T cells are exciting therapeutic tools for fighting cancer. Cytomegalovirus (CMV) based vaccines stimulate potent T-cell responses against cancer proteins. This project will use cutting-edge molecular biology and imaging to develop and test CMV-based cancer vaccines engineered to manipulate host immune responses to induce maximal immune responses.
Lead Supervisor: Professor Ian Humphreys.
HCMV is one of the most promising vaccine vectors for inducing immune responses against pathogens and cancer. However it’s unclear how these responses are induced. We will combine cutting-edge proteomics with functional immunology to determine how HCMV induces such strong responses, enabling us to generate optimised vaccine vectors.
Lead Supervisor: Dr Richard Stanton.
Radiotherapy (RT) uses ionizing radiation to kill cancer cells directly. It is likely that RT induces immune responses which also contribute to control of cancer. We will determine the impact of RT on immune activity in patients before, during and after RT. Findings will be used to design new trials aimed at combining RT with immunotherapy.
Lead Supervisor: Professor Awen Gallimore.
The human body is colonized by trillions of bacteria. These are generally harmless but can become a serious threat to human health. This project will investigate, for the first time, a specific protein that supports bacterial residence in the nose and throat. This protein also helps these bacteria to invade the body and evade the immune system to cause dangerous infections. Understanding the activity of this protein provides new insights into pathogenic bacteria.
Lead Supervisor: Dr Paul Curnow.
Drugs that block cytokine activity have revolutionised the treatment of rheumatoid arthritis, but ~40% of patients show inadequate responses 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 inflammation to support precision medicine.
Lead Supervisor: Dr Gareth Jones.
Ageing populations have increased disease susceptibility, partly due to deteriorating immunity. We will use novel drugs to re-program the immune system, focusing on macrophages, to reduce the progression of deadly lung diseases – and track this using clinical samples, in vitro/in vivo models, next generation sequencing and advanced imaging.
Lead Supervisor: Dr Chris Scotton.
Antibiotic resistance is a serious threat to public health. Its first step is often through signaling pathways that trigger the bacterium’s resistance mechanisms in response to a drug. This project will apply biochemistry, molecular biology and protein modelling to find inhibitors that block signaling and thus prevent activation of resistance.
Lead Supervisor: Dr Susanne Gebhard.
The release of free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (NOS) that cause an oxidative stress are a component of the host immune response during an infection, but they can also be damaging to the host tissue. This project will apply recently developed novel fluorescence techniques, and genetic and proteomic approaches to investigate the oxidative stress response during infection with a gastrointestinal parasitic nematode.
Lead Supervisor: Professor Steven Bull.
This project will investigate unexpected gene expression in cardiac macrophages that suggests these cells may undergo transdifferentiation during repair and regeneration of the heart. Cell-type specific CRISPR knockout of these genes and cutting-edge structural analysis using cryo EM will facilitate the investigation of the function of these genes in cardiac macrophages.
Lead Supervisor: Dr Rebecca Richardson.
Leucocyte trafficking can be modulated for therapeutic benefit in immune-mediated, inflammatory diseases including multiple sclerosis (MS) but individual patient responses are sub-optimal and variable. We will use biomimetic models and microfluidics to develop a personalised approach to drug selection in MS and identify novel therapeutic targets.
Lead Supervisor: Dr Claire Rice.
Cystic fibrosis (CF) is a genetic disorder characterised by chronic infection, inflammation, airway remodelling and mucus obstruction. Innate immune cells are key mediators of disease progression. Using in vivo live-imaging and genetics, we will dissect the molecular mechanisms underlying CF-related tissue damage and inflammatory dysfunction.
Lead Supervisor: Dr Helen Weavers.
This interdisciplinary project will develop a liposome formulation that nucleates hydroxyapatite and embeds antimicrobials in bone to prevent infection during fracture healing. It will be developed using in vitro and ex vivo techniques (across Cardiff), in vivo models (Southampton) and industrial and clinical involvement (BioPharma/Bristol).
Lead Supervisor: Dr Wayne Nishio Ayre.
This PhD will develop your microfabrication, material sciences, drug delivery and microbiology skills to engineer microneedles that porate the nail plate and create micro-channels through which specifically formulated medication is delivered deep into the nail to reach effective concentrations of antifungals with a novel platform for nail therapies.
Lead Supervisor: Dr M. Begona Delgado-Charro.
Exposure to infection before birth might impair the brain-protective effect of cooling therapy in newborn babies with hypoxic brain damage. We will investigate the impact of exposure to infection before birth on death & morbidity in 6000 cooled infants from the national database and on the immune response in a prospective cohort.
Lead Supervisor: Dr Ela Chakkarapani.
Strong anti-tumour immunity is thought to protect people from developing cancer and has been proven to limit disease progression in patients. This project will use cutting-edge immunological techniques to examine how forms of exercise influence immune-surveillance and overall immune-competency in healthy people and patients with prostate cancer.
Lead Supervisor: Dr James Turner.
This PhD will investigate, using a unique combination of experiments and simulations, how old red blood cells are cleared by our immune systems via phagocytosis. This has implications for a variety of conditions such as sickle-cell anaemia and thrombosis. Unlike most PhDs, this is an excellent opportunity to learn both the experimental and modelling sides of modern research. Full training in both these areas will form an important part of this project.
Lead Supervisor: Dr David Richards.
E. coli is the most important bacterial pathogen in Europe. Sepsis and antibiotic resistance rates caused by E. coli are soaring. We hypothesize that the cause of this is high gut carriage of virulent and resistant E. coli strains. Using the principle of my enemy’s enemy is my friend we will research the use of bacterial viruses to engineer the human microbiome towards non-virulent/antibiotic sensitive strains.
Lead Supervisor: Dr Mark Toleman.
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.
Fungal pathogens threaten our health and kill millions. In this project, we will deploy cutting-edge 3D chromatin genetics, mycology and bioinformatics to better understand how pathogenic fungi sense and adapt to the human host. Our goal is to open novel paths to interfere with fungal disease.
Lead Supervisor: Dr Hans-Wilhelm Nuetzmann.
Nonalcoholic steatohepatitis (NASH) is becoming the leading cause of liver transplantation in the UK, already affecting ~5% of the population, but with no approved treatment. The student will leverage our recent insights from artificial intelligence to discover new uses for approved drugs to treat NASH, accelerating efforts to bring successful therapies to the clinic.
Lead Supervisor: Dr YoYo Zhou.
Many serious diseases (e.g., meningitis, pneumonia, blood/wound infections) are caused by commensal bacteria that are common on the skin or in the guts of healthy people. However, questions remain about what makes good strains go bad. Using state-of-the-art genome analyses (including machine learning) and new laboratory techniques, we will identify the pathogenicity genes and evolutionary forces that cause harmless bacteria to become opportunistic pathogens.
Lead Supervisor: Professor Samuel Sheppard.
The ADP-ribosyltransferase toxins (ARTTs) represent a family of virulence factors that inhibit protein synthesis via ADP-ribosylation of essential intracellular elements and so facilitate the pathophysiology associated with a number of bacterial pathogens. This project aims to decipher the structural details of the toxin-host receptor interactions.
Lead Supervisor: Professor Randy Mrsny.
CD4+ T follicular helper (Tfh) cells provide vital protective immunity to infection and support B cell-driven antibody production yet these cells notably decline in animal models of sepsis. The PhD student will combine core immunological techniques and innovative gene profiling strategies to examine how Tfh cells become suppressed during sepsis.
Lead Supervisor: Dr James McLaren.
Antibiotic resistance is one of the greatest threats of our time, and finding new ways to eradicate drug-resistant bacteria would be truly ground-breaking. This project will explore the CRISPR-Cas9 genome editing system to target multi-drug resistant bacteria in the gut microbiome.
Lead Supervisor: Dr Stineke van Houte.
What makes a parasite a parasite? We have shown that genomes of parasitic nematodes are characterised by hotspots of virulence genes. This project will investigate the role of these ‘virulence hotspots’ in parasite – host interactions, the mechanism of gene co-regulation and the conservation of virulence hotspots across parasites.
Lead Supervisor: Dr Vicky Hunt.
B cells play a key role in type 1 diabetes (T1D). Using cutting edge single cell and Nanostring technologies, human B cells from pancreas, lymph node and skin samples from patients will be isolated, their transcriptome analysed and their immunoglobulin heavy and light chains expressed to allowed autoantibody analysis at the monoclonal level.
Lead Supervisor: Professor Kathleen Gillespie.
Coinfections can alter patient outcome, and efficacy of infection control, yet we have little understanding of even common and important coinfections. We will determine the effects of coinfection with three common and important human parasites, by following infections, health and treatment effects through time in very young children from Uganda.
Lead Supervisor: Dr Joanne Lello.
Understanding phenotype to genotype in humans is easier than bacteria because sexual reproduction decreases genome similarity. Bacteria reproduce asexually but occasional bacterial sex (recombination) shuffles the genome. Genomic analysis will be used to investigate the effect of recombination on discovering causal genes in disease phenotypes.
Lead Supervisor: Dr Lauren Cowley.
Fungi threaten our health, killing millions every year. New ways to stop the spread of fungal pathogens must be found. Here, we will deploy cutting-edge molecular biology, nanotechnology and imaging approaches to understand how fungal receptors function, aiding the design of novel approaches to impede the spread of drug-resistant pathogens.
Lead Supervisor: Dr Neil Brown.
CD8+ T and natural killer (NK) cells protect us from intracellular pathogens and cancers. This project aims to determine pathways that can drive the growth of particular types of NK and CD8+ T cells that are optimised to provide better protection from disease. We will use leukaemic cells and human cytomegalovirus as systems of study.
Lead Supervisor: Dr Eddie Wang.
Bronchopulmonary dysplasia (BPD) is the main cause of respiratory illness in ex-preterm children. With many associated morbidities, it makes a considerable demand on the health services. We propose to use Volatile Organic Compounds (VOC) to identify metabolic markers of respiratory morbidity in the ex-preterm population and potentially identify new therapeutic targets.
Lead Supervisor: Dr William Watkins.