Cohort 1 was the first group supported by the Gw4 BioMed MRC DTP. Below you can read about the projects and research interests of each student.
The neural network basis of essential tremor
I completed a BSc in Psychology at the University of Exeter, and an MSc in Neuropsychology at the University of Bristol. Whilst studying at the University of Bristol I was involved in research examining the effect of alcohol consumption on risky decision making. Following my studies, I worked as a research assistant at the University of Bristol. This work involved testing hypotheses that pleasing fragrances can influence emotional processing and behaviour, due to olfactory pathways to brain regions associated with motivation, reward, emotion and emotional decision making. Thanks to being awarded the MRC GW4 Biomed DTP, I am currently completing a PhD at the University of Bristol. My PhD project is grouped within the DTPs “Neuroscience and Mental Health” theme, and aims to examine the neural processes underlying a common movement disorder known as Essential Tremor. Using mathematical analysis of electrophysiological data, the projects aims to distinguish underlying neural networks contributing to Essential Tremor and Parkinson’s disease.
Investigating the Role of RNA Binding Proteins and Modulators of Mitochondrial Function in Neurodegenerative Disease
Using molecular biology techniques in human brain tissue and cell lines, I investigated an RNA binding protein called SAFB1 and its role in neurodegenerative disease especially polyglutamine disorders. In the second part of my thesis, I screened a library of drug compounds, leading to the identification and validation of a compound which improves mitochondrial health in-vitro. The drug may be a future candidate therapeutic agent for neurodegenerative conditions such as Parkinson’s disease.
Chaperones: mediators of the switch from commensal to pathogen?
Having completed my MSci Biochemistry at King’s College London, I am now part of the Diezmann lab at the University of Bath. Although the majority of the population have fungi of the Candida genus growing harmlessly on or in their body, for people with impaired immunity Candida can become pathogenic, with more than 50% of patients with systemic Candida infections succumbing to the disease. My project aims to better understand the interaction of the host with fungal Hsp90, a protein which plays an essential role in Candida virulence. This information may form the basis for new therapeutic drug targets.
Sphingosine-1-phosphate receptor 1 signalling in bacterial-macrophage interactions: exploring novel anti-bacterial strategies using immunomodulatory therapeutics
This project investigated the G-protein coupled receptor sphingosine-1-phosphate receptor 1 and identified several important regulatory roles it plays in mediating the interactions between macrophages and the important human pathogens Staphylococcus aureus and Pseudomonas aeruginosa.
Triggered bacteriophage release for treatment of wound infection
I am currently undertaking my first year of my PhD at the University of Bath and Cardiff University. My research falls under the Infection, Immunity and Repair (IIR) theme, and focuses on developing a prototype wound dressing for the treatment of bacterial infections. Ultimately, I wish to develop a wound dressing which releases bacteriophage (viruses which infect bacteria) into the wound in response to a ‘trigger event’ or stimuli, thus giving a burst release of bacteriophage only when required. This allows for the early treatment of the infection, which could prevent more serious complications such as septicaemia, and could also potentially lessen the likelihood for prescription antibiotics.
Hitting a moving target: The role of peptide-HLA flexibility during autoimmunity, transplant rejection, cancer and pathogen detection
I studied BSc (Hons) Biomedical Science at the University of Reading from 2013, graduating in 2016 with first class honours and having completed my dissertation work in endocrinology under the supervision of Professor Phil Knight. From 2016 I started as a GW4 MRC PhD student based at Cardiff University School of Medicine, in collaboration with Bath University. I am under the Infection, Immunity, and Repair division and supervised by Dr David Cole and Professor Andrew Sewell. My project aims to understand HLA-1 flexibility and its role in infection and autoimmunity.
Sites of active gene regulation in the developing human brain and their role in neuropsychiatric disorders
My research theme is Neuroscience and Mental Health. I will be working at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University with Dr Bray and Dr Hill and at University of Exeter, with Prof Mill’s epigenetics group. For my project, I will use ATAC-seq and bioinformatics techniques to identify regions of the genome that regulate gene expression in the developing human brain. I will then integrate my data with other genomic datasets including those from studies of neuropsychiatric disorders to help elucidate genetic risk mechanisms for these conditions.
Defining the contribution of dorsal vagal complex astrocytes to food intake
I used chemogenetics, electrophysiology, immunohistochemistry and in vivo behavioural assays in mice to investigate the role of non-neuronal cells in the brain’s control of food intake.
Behavioural susceptibility to obesity in young adults: genetic and environmental determinants of eating behaviour
I am a Dietitian and a Nutritional Epidemiologist. I hold a BSc in Nutrition and Dietetics from Harokopio University (Greece) and an MSc in Epidemiology and Public Health from Wageningen University (The Netherlands). Currently I am a PhD student at the Centre for Exercise, Nutrition and Health Sciences of the University of Bristol, supervised by Dr Laura Johnson (University of Bristol), Professor Tim Frayling (University of Exeter) and Dr Laura Howe (University of Bristol). My project focuses on the pathways leading from a series of genetic and environmental determinants to specific eating behaviours and, over time, to obesity, using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC). I also maintain a strong interest in dietary assessment methodology and teaching.
Relationship between synaptic dysfunction and degeneration in a rodent model of dementia
I obtained a BSc in Biochemistry (Pharmacology) from the University of Surrey. Since graduating, I have worked as a Molecular Pathologist at Eli Lilly and Company. I am now undertaking a PhD based at the University of Exeter and the University of Bristol in the theme of Neuroscience and Mental Health. My project will focus on dementia research, exploring the relationship between synaptic dysfunction and degeneration in a mouse model of dementia using whole-cell electrophysiology recordings and two-photon imaging.
Defining Mechanisms of T Cell Suppression in the Tumour Microenvironment
I am based in the Henry Welcome Building at Cardiff University under the Immune, Infection and Repair theme. My research is focused on defining the mechanisms by which anti-tumour T cell responses are suppressed in the tumour microenvironment. Cytotoxic T cells (CTL cells) have the ability to recognize and eliminate tumour cells however these efforts are largely suppressed in the tumour microenvironment. Using a combination of in-vivo and imaging approaches, my PhD project will explore how a subset of T cells termed regulatory T cells (which are highly enriched within tumours) suppress anti-tumour CTL responses. Understanding how anti-tumour responses are suppressed will provide useful in the design of new immunotherapeutic strategies for cancer treatment.
Newborn Brain Injury: The role of Glutamate Transport regulation
I am based in both Bristol and Cardiff, and my PhD falls into the Neuroscience and Mental Health research theme. I am interested in the role of glutamate transport in newborn brain injury. Glutamate is the main excitatory neurotransmitter in the brain and my research focuses specifically on the main glutamate transporter, which re-uptakes glutamate from the synaptic cleft following signalling, making sure it does not build up and cause injury. The hypothesis is that a mixture of genetic and environmental factors interact through epigenetic effects and affect the ability to dynamically regulate this transporter, making some babies more vulnerable than others when they experience hypoxia (e.g. due to birth asphyxia or prematurity). The overarching aim is to use genetic, epigenetic and neuroimaging information to develop neuroprotective strategies targeting the glutamate transport pathway that can protect the brain of animal models initially and of newborn babies in the future. This is a public health matter as newborn brain injury is currently the leading cause of neurodisability in childhood.
Identifying Novel Blood Biomarkers of Alzheimer’s disease
I am a PhD student at the University of Exeter Medical School, under the supervision of Dr Katie Lunnon (Exeter), Dr Daniel van den Hove (Maastricht), and Dr Liz Coulthard (Bristol). I graduated with a Research Master in Fundamental Neuroscience from Maastricht University (the Netherlands), where I had a particular interest in the epigenetics of Alzheimer’s disease. My PhD project, in the theme of Neuroscience and Mental Health, focuses on identifying novel blood biomarkers of Alzheimer’s disease. During my PhD I will integrate genome-wide genetic, epigenetic and gene expression measures in blood from Alzheimer’s disease patients with detailed clinical, epidemiological and neuroimaging data with the aim to identify unique biomarkers for AD.
William David Thompson
Using Mendelian Randomisation to investigate the association between intra-uterine factors and foetal growth
I am based at the RILD building at the Royal Devon and Exeter Hospital (though my project is with the University of Exeter). I am part of the Public Health research theme and my project is “Using Mendelian Randomisation to investigate the association between intra-uterine factors and foetal growth”. Numerous things influence birth weight (like diabetes and maternal smoking). However, whether a factor actually causes lower or higher birth weight or is being confounded by other things is often unclear. Mendelian Randomisation acts as an alternative to an RCT, by investigating whether genes associated with a factor (like blood glucose) are also associated with an outcome (like birth weight). As genes are believed to be distributed randomly in the population, this can help avoid confounding.
The role of sensorimotor incongruence in pathological pain
I looked at how people with painful conditions might be using information from their senses, and about movement, differently to those without pain, as this is theorised to contribute to the maintenance of certain conditions. For instance, I looked at the influence of pain on how the brain represents the shape and size of the body, and its surrounding space is updated. To test this idea, I conducted experiments with people with Complex Regional Pain Syndrome, and compared them to pain-free individuals.