About the Project
Genetic risk factors are highly significant in determining susceptibility to a range of psychiatric disorders including anxiety, depression and schizophrenia. Many of these psychiatric risk factors cluster around genes involved in synaptic function and plasticity but we know relatively little about the core features of synapses that are disrupted and how these lead to cognitive impairments common to many of these conditions.
Emerging evidence indicates that many key psychological processes such as perception, memory and adaptability rely on dendritic signalling events generated by the interaction of multiple synapses on single neurons. These dendritic signals are extremely sensitive to neural network perturbations caused by genetic mutations to synaptic proteins or changes in brain state mediated by neuromodulators such as acetylcholine or serotonin.
We have discovered that the genetic risk factors Dlg2 and Grin2A, which are associated with schizophrenia, autism and intellectual disability, disrupt dendritic signalling and synaptic plasticity (PMID: 35115661). In this project we aim to determine how these disrupted neuronal processes lead to impairments in flexible neuronal representations of behaviour and whether they may be rescued by targeting these specific processes. In this way we will directly link biological processes to cognitive impairments observed in psychiatric disorders and develop practical strategies for treatment.
The project will test these hypotheses using transgenic animals bearing mutations in the synaptic protein Dlg2 (Hall, Wilkinson). The project will first determine how dendritic calcium signalling is impaired in these animals using electrophysiology coupled with imaging of synaptic and dendritic calcium signals, techniques routinely used in the Mellor and Ashby groups (PMID: 26758963, 30242046). The project will then determine how hippocampal representations of spatial features adapt during changing environmental conditions by measuring hippocampal place cell activity using 2-photon imaging during animal exploration of a virtual reality environment, using early career researcher Witton's expertise. We will test whether reduction in Dlg2 expression impairs the flexible representation of changing environments at neuronal and behavioural levels. Finally, the project will test whether impairments in neuronal representations and behaviour may be rescued by application of clinically relevant drugs such as muscarinic receptor agonists or psychedelics that target serotonin receptors. The ultimate goal will be to find out if manipulating dendritic signalling using pharmacological tools is capable of changing behavioural outcomes in adult animals. This will form the basis of future therapeutic strategies for the treatment of psychiatric disorders.
The student will be trained in Bristol firstly in dual electrophysiology and 2-photon imaging performed in ex vivo brain slices and then in 2-photon imaging in vivo and animal behaviour paradigms developed in Cardiff, Exeter and Bristol. Aligned with this the student will be trained in complex data analysis and manipulation of virtual reality environments. Our collaboration with Dan Dombeck's group (www.dombecklab.org) offers the opportunity to learn from world leaders in virtual reality behaviour in rodents. In addition, the project can also be extended to use computational models to predict the likely outcome of dendritic signalling perturbations on behaviour through our collaborations with Cian O'Donnell (Ulster and Bristol) and Claudia Clopath (Imperial). The student will be encouraged to choose which approaches best suit their interests and skills and shape the project accordingly.
Through our collaborations with pharmaceutical companies including Compass pathways, SoseiHeptares, Lilly and Takeda we have access to novel drug pipelines that we can test. For example, Compass have shown psilocybin is effective in depression and SoseiHeptares have a suite of muscarinic receptor ligands in development for clinical trials in schizophrenia (PMID: 34822784).
How to Apply
A list of all the projects and how to apply is available on the GW4 BioMed website at gw4biomed.ac.uk. You may select up to 2 projects and submit one application per candidate only.
Please complete an application to the GW4 BioMed3 for an 'offer of funding'. If successful, you will also need to make an application for an 'offer to study' to your chosen institution later.
Please complete the online application form linked from our website by 5.00pm on Wednesday, 21st October 2026. Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the GW4 BioMed website for details and updates. If you are shortlisted for interview, you will be notified from Tuesday, 22nd December 2026. Interviews will be held virtually on 26th and 27th January 2027. Studentships will start on 1st October 2027.
Further Information
For informal enquiries, please contact GW4BioMed@cardiff.ac.uk
For project related queries, please contact the respective supervisors listed on the project descriptions on the GW4 BioMed website.
Funding Notes
These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21,805 p.a. for 2026/27, updated each year).
Additional research training and support funding of up to £5,000 per annum is also available.
This is a Preview Listing…
You must sign in to see the full job description, and to apply.
Manage / Upgrade this job to a Full Job Listing.
Find Your Best Opportunity
Tell them AcademicJobs.com sent you!