The details of the available projects for the Infection, Immunity & Repair theme are outlined on this page. You can find other projects on the Infection, Immunity & Repair and Population Health pages. A full list of our available projects can be downloaded below.
For full project descriptions, including contact details for the lead supervisor, click the download link by the project title.
Applications to the GW4 BioMed MRC DTP will be accepted via this online survey until 5 pm on 23rd November 2020. For guidance on the application criteria and decision timeline, please see the information here.
This project will investigate the effects of antidepressant withdrawal on neural markers of reward and emotion processing using event-related potentials in a longitudinal study of patients in primary care. We will also test whether changes in neural markers early in the withdrawal process can be used to predict later depressive relapse.
Lead Supervisor: Dr Katherine Button
Drug abuse has serious adverse neuronal effects leading to major mental health issues. In this interdisciplinary research, we will apply a range of advanced detection methods to assay prison and police samples from areas of deprivation in the South West. Using outcomes data, we will research the mental health and cognitive consequences of drug use in prison and aim to track how this predicts social and psychological functioning following release.
Lead Supervisor: Professor Stephen Husbands
Alzheimer’s disease has a significant heritable component, yet we know little about this genetic risk affects the living human brain. The project will incorporate bioinformatic approaches using neuroimaging, genomic and clinical health record data to understand why we see increased brain cell death in individuals with heightened genetic for Alzheimer’s disease.
Lead Supervisor: Dr Thomas Lancaster
Starting from an initial hit sequence, we will screen small ultra-stable lasso peptide libraries, to identify members that block alpha-synuclein (αS) toxicity associated with Parkinson’s disease. These highly structured molecules can resist breakdown, penetrate biological membranes, and are target selective. We will inhibit αS-associated toxicity using a powerful screen that searches millions of lassos inside live cells to identify those that restore viability.
Lead Supervisor: Professor Jody Mason
The effect of neurodegenerative conditions, such as Alzheimer’s disease, on neuronal ion channel properties is not well understood. This project will combine sophisticated inverse mathematical methods with brain slice electrophysiology to quantify changes to specific ion channels in dementia. This interdisciplinary approach will provide important insights into neurophysiological dysfunction.
Lead Supervisor: Professor Alain Nogaret
Neurophysiology and health psychology research identified the mechanisms of response to stress, with the allostatic load pointing to a physiological ‘wear and tear’ leading to dysregulation and poor health. This project will combine expertise in microfluidic diagnostics and neurophysiology to deliver a transformative biosensor profiling key stress hormones and inflammatory biomarkers, for monitoring response of the nervous, endocrine and immune system to stress.
Lead Supervisor: Dr Nuno Reis
Disruption to sleep causes dementia pathology and symptoms. New mobile technology has made it possible to measure brain activity during sleep remotely, in patients’ natural home environments. The studentship will harness this new technology to understand the role of sleep in early dementia, bringing together clinical neurologists, neuroscientists, biomedical mathematicians and an industrial partner to provide a unique, ambitious and interdisciplinary project.
Lead Supervisor: Dr George Stothart
This PhD project will ask: Can we isolate the relationships between cannabis use, tobacco use and psychiatric disease through triangulation of data from multiple data sources (Cohort data, brain imagining data), and across statistical methods that differ in their ability to make causal links?
Lead Supervisor: Dr Gemma Taylor
Adult neural stem cells produce neurons and have great potential in regenerative medicine to limit neuronal damage and functional loss. This project will systematically define novel KAP1-long non-coding RNA chromatin regulatory complexes needed for neuron production that may be targeted to develop new treatments for neurodegenerative disorders.
Lead Supervisor: Dr Keith Vance
There has recently been an increase in overdose deaths where both opioids and illicit benzodiazepines (BZDs) are present. We wish to establish first how heroin users view the advantages and dangers of taking these drugs and then to assess in laboratory studies the interactions between novel BZDs and opioids at the cellular and whole animal levels to determine the mechanisms by which they might interact to heighten the likelihood of overdose.
Lead Supervisor: Professor Matthew Hickman
Integrating genetics, psychiatry, neural network physiology and machine learning, this project will combine patient EEG and mouse high-density electrophysiology to determine whether sleep disruption is a “canary in the coalmine”, predicting psychosis and/or memory impairments in young people at high risk of schizophrenia.
Lead Supervisor: Professor Matt Jones
Although individuals with dementia experience sleep disruption, it is unclear whether sleep disruption is a risk factor for dementia, or whether sleep disruption is a result of dementia pathology. The aim of this project is to use causal methods applied to a life course epidemiology approach to investigate whether sleep quantity or quality across the life course is a risk factor for dementia progression, or vice versa.
Lead Supervisor: Dr Liam Mahedy
This interdisciplinary PhD project will provide training in advanced epidemiological and statistical methods. Data from a large birth cohort will be used to improve understanding of the relationship between adverse childhood experiences (ACEs) and mental health outcomes (depression and self-harm). This will include investigation of specific ACEs and ACE profiles, the role of timing, chronicity and recency of exposure, and identification of potential mechanisms.
Lead Supervisor: Dr Becky Mars
Genetic risk factors for psychiatric disorders are clustered around genes that regulate synaptic function and adaptation indicating common disrupted biological processes. In this project, we will uncover how one of these genes (Dlg2) perturbs a core feature of synaptic signalling to increase susceptibility to early life stress, and leads to abnormal cognitive processing.
Lead Supervisor: Professor Jack Mellor
Many genes coding for synaptic proteins have been linked to neuropsychiatric disorders like autism and schizophrenia. One puzzle is why these various genetic mutations lead to overlapping cognitive symptoms. This project will tackle the problem using data-driven computational models of biochemical signalling at synapses, focusing on the role of Cacna1c L-type calcium channels. It will be a mix of numerical simulations, mathematical analysis, and data analysis.
Lead Supervisor: Dr Cian O’Donnell
Schizophrenia is a severe psychiatric disorder with an unclear biological basis. This project will combine single cell RNA sequencing technology with the latest data on genetic risk factors for schizophrenia to identify cell types and mechanisms within the developing human brain mediating genetic risk for the condition. The project will provide training in state-of-the-art laboratory and bioinformatic techniques for analysing cellular gene expression.
Lead Supervisor: Dr Nick Bray
Genetic variants associated with risk for psychiatric disorders are located in the vicinity of genes involved in synaptic plasticity. There is evidence that these variants act through regulatory processes affecting gene expression, including the epigenome. This project will look at whether epigenetic processes involved in regulating plasticity are important in conferring risk to psychiatric disorders such as schizophrenia.
Lead Supervisor: Professor Jeremy Hall
In the UK ~8% of women are prescribed antidepressants to reduce symptoms of depression in pregnancy. This project will ask whether antidepressants restore normal mood in a novel preclinical model of prenatal depression, and apply comparative bioinformatics to human placenta to examine the risks and benefits of taking antidepressants in pregnancy.
Lead Supervisor: Professor Rosalind John
Using advanced imaging and novel mathematical approaches, we will identify spatio-temporal brain networks that show altered dynamics in young adults with genetic risk for Alzheimer’s disease. The PhD will provide grounding in network neuroscience — an evolving field using network theories to study the brain across multiple scales and modalities.
Lead Supervisor: Dr Jiaxiang Zhang
Circadian rhythm times our sleep, and its disruption exacerbates Alzheimer’s disease (AD) pathology. The brain’s master clock uses GABA for circadian timekeeping. GABA signals are affected in AD, but the effect on clock function is unknown. We will study how GABA drives excitability in healthy and AD mouse clock neurons, to restore clock function and improve health.
Lead Supervisor: Dr Mino Belle
Like drugs of abuse, food activates parts of the brain associated with rewarding and pleasurable feelings. People living with obesity show changes in activity of these brain areas. Using mice as a model system, this project will investigate how controlling the activity of brain cells called astrocytes alters motivation and food preference, which may contribute to obesity.
Lead Supervisor: Professor Kate Ellacott
The environmental causes of the onset and persistence of mental illnesses are not well understood. This project will develop a new approach that is founded in information ecology. We will develop computer models of learning and decision-making that capture the main features of depression, anxiety, PTSD, OCD, and related harmful behaviour.
Lead Supervisor: Dr Andrew Higginson
During this PhD, you will be one of the very first people to study the epigenetics of Huntington’s disease. You will determine the first-ever comprehensive brain microRNA profile and then evaluate the most promising microRNAs in cell models. This project will combine the exciting areas of epigenetics, bioinformatics and molecular biology. It will lead to improved mechanistic understanding and suggest novel drug targets to treat this devastating condition.
Lead Supervisor: Dr Anna Migdalska-Richards
Exposure to chronically stressful situations is a major risk factor for clinically diagnosed depression. The brain integrates stress signals through the limbic system, the activation of which ultimately leads to glucocorticoid release. This project will investigate how astrocytes fine-tune processing of stress signals in the limbic system and how glucocorticoids in turn feedback to astrocytes to ensure an appropriate stress response.
Lead Supervisor: Dr Valentina Mosienko
Alzheimer’s disease (AD) is characterised by the malfunction of neural circuits. Recent evidence suggests that this is initiated by an imbalance between excitatory and inhibitory neuronal activity. This project combines cutting-edge mouse genetics, brain imaging and computational modelling to decipher how changes in inhibitory interneurons cause neural circuits to malfunction early in AD, providing an opportunity for early intervention.
Lead Supervisor: Dr Jonathan Witton