Applications for our 2020/2021 recruitment round have now closed. Please look out for more details for 2021/22.
Please find the details of the available projects for the Neuroscience and Mental Health 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.
Synthetic cannabinoid receptor agonists (SCRAs) can have serious adverse effects. This project involves research in a SCRA clinic to characterise dependence and withdrawal, and test a novel detoxification method. It provides training in laboratory techniques to identify SCRAs in drug and biological samples and relate these to clinical outcomes.
Lead Supervisor: Dr Tom Freeman.
With more people living longer there is a need to identify mechanisms that can moderate age-related declines in cognitive function. Animal models with naturally extended lifespans can highlight candidate mechanisms for potential therapeutic intervention. This project will develop a new, and unorthodox, insect model of ageing and cognitive decline.
Lead Supervisor: Dr Stephen Montgomery.
One third of those with major psychiatric disorders do not respond to standard therapies and are considered “treatment resistant”. This project will characterise the features of treatment resistance across three diagnoses (schizophrenia, bipolar disorder, major depression), by analysing health records and genetic data from thousands of patients.
Lead Supervisor: Professor James Walters.
This project applies advanced chemically- and mechanically-sensitive optical microscopy to glioblastoma, the most aggressive brain cancer in adults. We will investigate how cancer stem cells remodel their microenvironment to generate lipid metabolites that they use for energy support, and whether disruption of this process can stop tumour progression.
Lead Supervisor: Dr Florian Siebzehnrubl.
This PhD project will ask: Can we isolate the relationships between cannabis, tobacco and psychiatric disease through triangulation of data from countries that smoke cannabis with, and without tobacco, and across statistical methods that differ in their ability to make causal links?
Lead Supervisor: Dr Gemma Taylor.
Concussion is a mild traumatic brain injury that temporarily affects brain functioning, and is a major concern in sport. However, the subtle symptoms, such as slow thinking and reaction time, are currently hard to detect without lengthy clinical examinations. This PhD will validate a novel movement protocol to quickly and objectively identify concussions, combining leading clinical diagnosis tools, cutting-edge neuroscience, and technology.
Lead Supervisor: Dr Genevieve Williams.
Many genes coding for synaptic proteins have been linked to neuropsychiatric disorders like autism and schizophrenia. One puzzle is why these various mutations lead to overlapping cognitive symptoms. This project will address this using data-driven computational models of biochemical signalling at synapses, focusing on Cacna1c calcium channels.
Lead Supervisor: Dr Cian O’Donnell.
Despite evidence of highly flexible sensory-independent areas in the adult brain (e.g. visual word form area responding to tactile written language) it is still unknown how this rapid sensory-independent plasticity develops. This project will fill this gap in research and inform the development of early sensory interventions.
Lead Supervisor: Dr Karin Petrini.
Alzheimer’s disease (AD) involves amyloid-B and tau accumulation resulting in memory, sleep and circadian rhythm loss. How this occurs is unknown hampering the development of effective AD drugs. We aim to address this issue using a mixed model approach to study the effect of AD on circadian rhythms and sleep using flies, mice and computer models.
Lead Supervisor: Professor James Hodge.
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 these genes perturb a core feature of synaptic signalling to increase susceptibility to early life stress and lead to abnormal cognitive processing.
Lead Supervisor: Professor Jack Mellor.
There is a need for a reliable biomarker for Alzheimers disease (AD). Loss of neurones in the brain is a major feature of AD and precedes symptom onset. This project proposes to use neuron-specific epigenetic signatures to detect and measure the amount of circulating cell-free DNA of neuronal origin and explore its use as an AD biomarker.
Lead Supervisor: Dr Emma Dempster.
Genetic evidence implicates immune dysregulation in psychosis. A reduction in regulatory T-cells (Tregs) is consistently reported in patients with psychotic-mood disorder. We will test whether Treg depletion is associated with psychosis-mood relevant neurobehavioural phenotypes across species.
Lead Supervisor: Professor Lawrence Wilkinson.
Alzheimer’s disease (AD) is associated with increased oxidative stress in the brain. The Redox system that helps detoxify neurons is decreased in AD patients and likely contributes to symptoms and neurodegeneration. The PhD student will manipulate Redox genes in Drosophila and iPSC neuron models of AD to find new potential therapeutic targets.
Lead Supervisor: Dr Gaynor Ann Smith.
The main symptoms of Alzheimer’s disease (AD) are learning and memory loss. Remodelling of neural circuits through the formation and elimination of synapses is key to these cognitive processes. Recent evidence has revealed the importance of remodelling inhibitory synapses in cognition, but little is known about how this is affected in AD. We will study this using cutting-edge in vivo two-photon brain imaging.
Lead Supervisor: Professor Andrew Randall.
This mixed-methods interdisciplinary project investigates the mental health and wellbeing of teens in care. The project covers: 1) framework development on the emotional needs of these young people; 2) mapping of how mental health services respond, including when they transition to adult services; and 3) investigating the feasibility of targeting mental health within social care.
Lead Supervisor: Dr Rachel Hiller
This project will study the neural circuitry of mice with a chromosomal microdeletion that, in humans, greatly increases the risk of developingschizophrenia or ASD. The project will employ a combination of electrophysiology, optogenetics and behaviour to determine how impaired neural circuit function leads to impaired cognition.
Lead Supervisor: Dr Michael Craig
There is an unprecedented need for decentralised diagnostic tests able to measure levels of neuroendocrine and stress hormones. This interdisciplinary project will deliver a disruptive, global biosensing methodology for fingerprinting endocrine hormones and demonstrate its impact in endocrinology and health psychology.
Lead Supervisor: Dr Nuno Reis
Epilepsy is a common neurological disorder, frequently associated with memory problems. Surgery is potentially curative of seizures, but the impact on memory can affect quality of life more than seizures. This project will develop novel interdisciplinary tools to predict surgical outcomes on memory and seizures in people with epilepsy.
Lead Supervisor: Dr Denize Atan
Like drugs of abuse, food activates parts of the brain associated with rewarding and pleasurable feelings. People who are obese show changes in activity of this brain reward pathway. This project will investigate how controlling the activity of astrocytes alters motivation to eat and preference for “rewarding” foods which are high in fat and sugar.
Lead Supervisor: Dr Kate Ellacott
Using advanced imaging and novel mathematical approaches, we will identify spatio-temporal brain networks that show altered dynamics in adults with genetic risk for Alzheimer’s disease. The PhD will provide grounding in network Neuroscience — an evolving field using complex network theories to study the brain across multiple scales and modalities.
Lead Supervisor: Dr Jiaxiang Zhang
This project investigates how mutation of Ehmt1 in patients with the neurodevelopmental disorder, Kleefstra Syndrome (KS) leads to dysregulation of the miR-mediated gene regulatory network. It will use informatics, functional genomics and new CRISPR methodologies to analyse the gene regulatory network in patient derived induced pluripotent stem cells (iPSC).
Lead Supervisor: Professor Adrian Harwood
During this PhD, you will be one of the very first people to study the genome-wide epigenetics of Parkinson’s disease. You will determine the first-ever DNA methylation profile in distinct brain cell types of individuals with Parkinson’s. This will involve combining the exciting areas of epigenetics, genetics and bioinformatics. This work will lead to improved mechanistic understanding and suggest novel drug targets to treat this devastating condition.
Lead Supervisor: Dr Anna Migdalska-Richards
Abnormality of social interaction and motor coordination are the common symptoms of autism. Current data indicate that disruption to the JAKMIP1 gene results in autism phenotypes in mice. This project will focus on investigating disrupted neural processing in the cortex and cerebellum using integrated bioinformatics, molecular biology, and electrophysiology.
Lead Supervisor: Dr Asami Oguro-Ando
Cognitive flexibility allows animals to navigate complex social environments. Responding inappropriately, or inflexibly, to social or other cues is a hallmark of many mental disorders such as schizophrenia, autism, addiction and OCD. This project examines transcriptomes in key brain regions at critical periods to determine the molecular bases of flexible behaviour.
Lead Supervisor: Professor Anthony Isles
The loss of memories of places is an early symptom of Alzheimer’s disease (AD). These “spatial memories” are generated by networks of space coding neurons, called place cells, in a key brain structure for memory called the hippocampus. This project will use cutting-edge in vivo brain imaging to discover how place cells become disrupted in AD, and attempt to treat this using drugs that target AD pathology.
Lead Supervisor: Dr Jonathan Witton
Behavioural pharmacology, in vivo imaging and transcriptomic/epigenetic approaches will be used to test the hypothesis that depression in pregnancy damages the placenta contributing to adverse behavioural outcomes for mother and offspring. Concurrently, the benefit/risk of antidepressants in pregnancy will be assessed in humans and a model system.
Lead Supervisor: Professor Rosalind John
Circadian rhythm times our sleep and its disruption can exacerbate Alzheimer’s disease (AD) pathology. The brain’s master clock uses GABA for circadian timekeeping. GABA activity is 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 quality of life.
Lead Supervisor: Dr Mino Belle
The medial prefrontal cortex (mPFC) forms the hub of a brain circuit critical for associative recognition memory. The role of mPFC inhibitory interneurons in associative memory is not known. This project will combine behavioural, opto/chemogenetic, circuit mapping and synaptic physiology techniques to determine how different interneurons control different phases of associative memory.
Lead Supervisor: Professor Zafar Bashir
People with asthma and COPD live with chronic breathlessness, but current treatments overlook the psychological disease aspects. This project will use cutting-edge cognitive neuroscientific theory and psychological experimental methodologies to develop a ‘Bayesian Brain’ model of breathlessness that will inform and improve clinical treatment.
Lead Supervisor: Dr Ben Ainsworth