Neuroscience & Mental Health Projects

The details of the available projects for the Neuroscience & Mental Health theme are outlined on this page. You can find other projects on the Infection, Immunity, Antimicrobial Resistance & Repair 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.

Using brain stimulation to understand contributions of higher-level motor function to pathological pain

Pain in a given area of the body could be related to how the area is represented in a part of the brain that controls movement (primary motor cortex). However, treatments based on changing this representation have limited success. To work towards better treatment, this project will use cognitive testing and brain stimulation to test the possibility that other brain areas responsible for planning, interpreting, and understanding movement are impaired in chronic pain.

Lead Supervisor: Dr Janet Bultitude
Institution: Bath

Understanding the neural mechanisms of antidepressant withdrawal and links with depressive symptoms, reward processing and relapse

This project will investigate the effects of antidepressant withdrawal on neural markers of reward and emotion processing using event-related potentials (ERPs) in a longitudinal study of patients in primary care. We will also test whether changes in neural markers early in the withdrawal process predict depressive relapse and investigate links between neural markers and mood changes, focusing particularly on experiences of reward in everyday life.

Lead Supervisor: Dr Katherine Button
Institution: Bath

Effects of cannabis on the adolescent brain and epigenetic aging

Adolescence is a critical neurodevelopmental period which may confer greater vulnerability to the effects of cannabis. To test this hypothesis, you will apply a range of advanced methods (structural MRI, diffusion MRI, brain aging, epigenetic aging) to a recently completed longitudinal study. You will work with young people to create a video resource informed by your results to create evidence-based drugs education and encourage youth engagement with science.

Lead Supervisor: Dr Tom Freeman
Institution: Bath

Advanced detection of synthetic cannabinoids used in prisons in the South West (GW4) region

Drug abuse can have serious neuronal adverse effects leading to major mental health issues. We will apply advanced detection methods to synthetic cannabinoid receptor agonists (Spice) in our interdisciplinary research project assaying HMP and Police samples. We will then research mental health and cognitive consequences of use of these drugs in prisons, using outcomes data to track how this predicts social and psychological functioning following release.

Lead Supervisor: Prof Stephen Husbands
Institution: Bath

Predicting the dementia-induced changes to neuronal ion channels: a combined experimental and in-silico approach

Channelopathies in which certain ion channels are over-expressed or absent occur in many neurological diseases. Currently, changes in neuronal function cannot be linked to underlying mutations in ion channel proteins. This interdisciplinary project will combine sophisticated computational methods with brain slice electrophysiology to quantify changes in specific ion channels in Alzheimer’s disease and provide important insights into neurophysiological dysfunction.

Lead Supervisor: Prof Alain Nogaret
Institution: Bath

Being in a child shoes: Assessing changes in parents’ empathy and perspective-taking by using a combination of virtual reality and EEG methods

Perspective-taking (cognitive awareness of another’s state) and empathy (emotional/affective response) are important for sensitive and constructive parenting. However, these constructs are difficult to induce and measure and their underlying brain mechanisms during parenting remain unclear. This project will use a combination of virtual reality, electroencephalogram (EEG) and self-report measures to examine changes in parents’ empathy to inform future interventions.

Lead Supervisor: Dr Karin Petrini
Institution: Bath

Implantable microchips for real-time monitoring of endocrine disorders

Measuring endocrine hormones is very challenging as the level of these hormones in blood can change very rapidly. This limits the ability to correctly diagnose patients with endocrine disorders and to research the interlinks between endocrine system, stress response and onset of chronic diseases. This project will use novel supramolecular chemistry embedded in a novel microchip to enable non-invasive real-time monitoring of key endocrine hormones.

Lead Supervisor: Dr Nuno Reis
Institution: Bath

Using mobile electroencephalography (EEG) and computational modelling to understand the role of sleep in disease progression in amnestic mild cognitive impairment

Disruption to sleep causes dementia pathology and symptoms. New mobile technology now makes it possible to measure brain activity during sleep remotely, in patients’ natural home environments. The project 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 studentship.

Lead Supervisor: Dr George Stothart
Institution: Bath

How does the schizophrenia risk gene, SETD1A, alter the early life development of brain circuits?

Schizophrenia is a severe neurodevelopmental psychiatric disorder with high heritability, but we don’t know how genetic variation leads to abnormal maturation of brain function. Disruption of the SETD1A gene is linked to elevated schizophrenia risk. In this project, we will investigate the cortical development of a mouse model of SETD1A deficiency using molecular, electrophysiological, imaging and behavioural techniques to link aberrant neurobiology to pathology.

Lead Supervisor: Dr Michael Ashby
Institution: Bristol

Developing individualized somatosensory stimulation tools to understand and manipulate dysfunctional network activity in dystonia

Dystonia is a movement disorder that causes involuntary muscle contractions and is challenging to treat. By combining EEG recordings with non-invasive somatosensory stimulation, this project will test the hypothesis that pathological synchronization of sensorimotor network activity causes motor symptoms. Data analyses and computational modelling techniques will be used to optimize stimulation protocols that aim to ameliorate dystonia symptoms.

Lead Supervisor: Dr Petra Fischer
Institution: Bristol

Improving health outcomes in Type 2 diabetes by stimulating positive behaviour change through virtual reality

Virtual reality technology has shown extensive potential to transform healthcare; from medical training during COVID-19 to rehabilitation and mental health care. This project will explore its value in improving health and wellbeing in people with type 2 diabetes. You will work closely with these individuals and learn to adapt technology to address health challenges, visit the NHS trusts and undergo a placement in industry to build cross-sector collaborations.

Lead Supervisor: Prof Julian Hamilton-Shield
Institution: Bristol

Modelling the role of L-type voltage-gated calcium channels (CACNA1C) in behaviour and mental health

CACNA1C regulates neuronal excitability underlying memory, sleep and circadian rhythms and has been associated with schizophrenia, autism, bipolar disorder and ADHD. CACNA1C blockers are prescribed for hypertension, pain, epilepsy and neurodegenerative disease. We propose to characterise CACNA1C disease variants in Drosophila using behaviour, electrophysiology, imaging, pharmacology and computational modelling to understand plasticity and pathology mechanisms.

Lead Supervisor: Dr James Hodge
Institution: Bristol

Menopause and depression: relationships and potential mechanisms

This project will apply cutting-edge causal inference methods to existing data from longitudinal population-based cohorts to advance understanding of the relationships and potential mechanisms linking menopause to an increased risk of depression. There is also an opportunity to analyse existing qualitative data exploring women’s experiences of the menopausal transition to add further understanding of the impacts on mental health.

Lead Supervisor: Prof Carol Joinson
Institution: Bristol

Sleep as a lens through which to predict psychiatric risk and translate mechanisms of neural network dysfunction in schizophrenia

Integrating genetics, psychiatry, neural network physiology and data science, 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: Prof Matt Jones
Institution: Bristol

In vivo Haematopoietic Stem Cell Gene Therapy for People with Friedreich’s Ataxia

Friedreich’s ataxia is an incurable neurological disorder, typically presenting in late childhood. Children born with the condition experience progressive accumulation of nervous system damage and neurological disability. The project will be to develop an in vivo gene therapy approach for people with Friedreich’s ataxia that offers the prospect of a universal, safe, and rapidly translatable treatment and a major advance for the genome editing field.

Lead Supervisor: Dr Kevin Kemp
Institution: Bristol

Novel immunologic mechanisms and treatment targets for depression

Emerging evidence implicates low-grade systemic inflammation in depression, but therapeutic advance will depend on identifying and validating immune proteins/pathways that are causally related to illness risk. This PhD will apply population and clinical randomised approaches, e.g., Mendelian randomization analysis and existing data/samples from clinical trials of immunotherapies, to examine the role of NLRP3 inflammasome and related biomarkers in depression.

Lead Supervisor: Prof Golam Khandaker
Institution: Bristol

Intergenerational transmission of self-harm thoughts and behaviours

This interdisciplinary PhD project will provide training in epidemiology, genetics, and advanced longitudinal methods. Data from two cohorts will be used to i) investigate the association between parent and child self-harm thoughts and behaviors ii) identify mediators and moderators that might inform preventative interventions and iii) explore the extent to which transmission is driven by shared genetic effects.

Lead Supervisor: Dr Becky Mars
Institution: Bristol

Linking neuronal function to mental health: How genetic risk factors impair cognitive flexibility and neural plasticity in psychiatric disorders

Genetic risk factors for psychiatric disorders are clustered around genes that regulate synaptic function and adaptation indicating common disrupted biological processes. We have revealed how one of these genes (Dlg2) perturbs a core feature of synaptic signalling. In this project, we will uncover how this leads to abnormal cognitive processing by directly measuring neuronal adaptations during tasks demanding cognitive flexibility.

Lead Supervisor: Prof Jack Mellor
Institution: Bristol

Regulation of stress response by astrocytes

Exposure to chronically stressful situations is a major risk factor for clinically diagnosed depression. However, some individuals are less susceptible to stress and resilient to developing serious mental health illness. This project will investigate how non-neuronal brain cells, called astrocytes, fine-tune responses to stress and discover novel molecular and cellular determinants of stress resilience.

Lead Supervisor: Dr Valentina Mosienko
Institution: Bristol

Exploring the early genetic origins of schizophrenia at the cellular level

Schizophrenia is a severe psychiatric disorder with an unclear biological basis. This project will combine single cell 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: Prof Nick Bray
Institution: Cardiff

The impact of common allele risk for schizophrenia on brain anatomy and function

Despite recent progress in our understanding of schizophrenia’s genetic grounds, little advance has been made in our understanding of its neurobiological mechanisms. This is partly due to our inability to uncover the effect of common allele risk for schizophrenia on the brain’s anatomy and function. We will apply innovative methods to identify gene-sets that can best predict brain phenotypes associated with schizophrenia.

Lead Supervisor: Dr Xavier Caseras
Institution: Cardiff

Investigating the neurobiology underlying dissociable effects on attention and motor impulsivity using a new mouse model: implications for X-linked ichthyosis and ADHD subtypes

In mice and humans loss-of-function of the steroid sulfatase (STS) enzyme results in inattention but enhanced motor response inhibition; we aim to understand the neurobiology underlying this dissociation using a new mouse model. The project will develop behavioural neuroscience research skills, will have direct clinical relevance to X-linked ichthyosis (STS deficiency), and will signpost mechanisms associated with Attention Deficit Hyperactivity Disorder subtypes.

Lead Supervisor: Dr William Davies
Institution: Cardiff

Interrogating the epigenetic links between prenatal adversity and increased risk of autism, schizophrenia and depression

Adversity-driven epigenetic changes early in life may increase the risk of mental illness in a sex-specific manner. This study will apply state-of-the art ‘omic approaches to define transcriptional and epigenetic signatures resulting from exposure prenatal depression, and compare to signatures present in samples from autism, schizophrenia and depression patients to provide novel insights into pathophysiology, and provide targets for manipulation.

Lead Supervisor: Prof Rosalind John
Institution: Cardiff

Long-term Neural Embedding of Childhood Adversity in the Avon Longitudinal Study of Parents and Children (ALSPAC)

This project will utilize a unique large-scale data set to examine the link between prospectively ascertained adversity during childhood and adolescence and cutting-edge multi-modal neuroimaging measures of both the structural and functional connectome, providing novel insights on the mechanisms through which childhood adversity becomes neurally embedded and influences mental health and cognition.

Lead Supervisor: Prof Andrew Lawrence
Institution: Cardiff

The role of neural stem cells and neurogenesis in regulating body weight

We will investigate the role of neural stem cells and new neurons in the control of body weight. We will determine how diet-induced obesity affects neural stem cells, neurons and glia in the hypothalamus, a part of the brain which regulates basic physiological functions such as appetite. This project will provide advanced training in methods ranging from electrophysiology, calcium imaging, time-lapse live-cell imaging, and single-cell RNA sequencing.

Lead Supervisor: Dr David Petrik
Institution: Cardiff

Investigating novel types of irritability using a developmental and genetic approach

Severe childhood irritability is disruptive, impairing, a common reason for mental health service referral and a major treatment challenge. It is uncertain if irritability is a behavioural, neurodevelopmental or mood problem. This PhD will use longitudinal, population cohorts to examine irritability across development and test the hypothesis that there are different types of irritability, differentiated by developmental course, genetic and environmental aetiology.

Lead Supervisor: Dr Lucy Riglin
Institution: Cardiff

Analysing the differentiation and function of the neurons damaged in Huntington’s Disease

Striatal medium spiny neurons (MSNs) bear the brunt of pathology in Huntington’s disease (HD). You will use a range of in vitro and in vivo cell, molecular genetic and whole animal techniques to dissect how the transcription factors FoxP1 and Mef2C function in MSNs differentiation. This knowledge is key for optimising MSN differentiation protocols from stem cells for disease modelling and cell therapies, and understanding the degeneration of MSNs in HD.

Lead Supervisor: Prof Anne Rosser
Institution: Cardiff

Metabolic ageing signatures in Alzheimer’s disease models

Age is currently the biggest risk factor for developing Alzheimer’s disease. It is not well understood how ageing impacts hallmark Tau and amyloid pathology in the brain and neuronal function. The PhD student will investigate how age related shifts in mitochondrial and peroxisomal metabolism impact the behaviour and neurodegeneration seen in Drosophila models of Alzheimer’s disease. The student will learn cutting edge imaging techniques and bioinformatic approaches.

Lead Supervisor: Dr Gaynor Smith
Institution: Cardiff

Developing zebrafish models of drug-induced seizures and childhood neurodegenerative epilepsies for use in drug development

Epileptic seizures can be caused by medications or genetic changes. This project will characterise seizure activity in zebrafish to identify seizure-causing drugs, and to specific seizure phenotypes in childhood epilepsy models to create a platform for drug discovery. The developmental basis for seizures in these epilepsies, and effects of drugs on neural connectivity, will be investigated to understand disease mechanisms and identify novel therapeutic targets.

Lead Supervisor: Dr Helen Waller-Evans
Institution: Cardiff

Developing a new blood test to revolutionise diagnosis and management in patients with motor neurone degenerative disorders

Motor neurone disease (MND) affects the brain and nerves, causing weakness and paralysis that worsens over time. Currently no test is available to efficiently diagnose or determine risk of developing MND. This PhD studentship combines cutting edge genomic studies with newly developed lipid analytical methods, to develop a revolutionary new cross-cutting blood test for use in the clinical setting to aid diagnosis and therapy development for MND patients.

Lead Supervisor: Dr Emma Baple
Institution: Exeter

Epigenetic profiling in Parkinson’s disease: novel mechanisms and drug targets

During this PhD, you will be one of the very first people to study the epigenetics of Parkinson’s disease. First, you will determine the first-ever comprehensive microRNA profile in different brain regions. Second, you functionally evaluate the most promising microRNAs in relevant cell models. This will involve combining the epigenetics, bioinformatics and molecular biology. This work will lead to improved mechanistic understanding and suggest novel drug targets.

Lead Supervisor: Dr Anna Migdalska-Richards
Institution: Exeter

Exploiting lipid binding proteins to tackle neurological disorders

This multi-disciplinary project combines cutting-edge molecular cell biology, neurobiological, and biochemical (lipid analysis) approaches to reveal novel links between organelle membrane proteins, lipid metabolism, and neurodegenerative disorders. It will unveil new biomedical principles, the functions of novel lipid-binding proteins, and new avenues for the treatment of neurodegenerative disorders.

Lead Supervisor: Prof Michael Schrader
Institution: Exeter

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