towards treatments targeted at biology.
This PhD tests a simple but powerful idea: that genetically diverse risk factors converge on the same brain cells, the medium spiny neurons (MSNs) of the striatum. The striatum controls movement, motivation, reward and habit learning and is increasingly implicated across psychiatric conditions, yet it has been overshadowed by decades of cortex-focused research. Our recent human stem cell work shows that reciprocal 16p11.2 copy number variants disrupt MSN development and shift the balance of striatal neuron subtypes, providing proof-of-principle that genetic risk produces measurable MSN phenotypes. This project asks whether risk genes from across disorders converge on these same MSN mechanisms.
The student will curate risk genes across schizophrenia, autism spectrum disorder, developmental disorder and bipolar disorder, spanning common variants, rare coding variants and copy number variants, and test which are enriched in striatal MSNs and their progenitors, using our own single-cell transcriptomic datasets alongside published human brain atlases. They will build a cross-disorder map of convergent MSN risk, then test whether these convergent signatures predict basal-ganglia-relevant traits (motor, cognitive and reward-related measures) in large population and patient cohorts, including UK Biobank. This defines whether convergence on MSNs is shared across disorders or is specific to particular genetic mechanisms.
To show that the prioritised genes really do act in MSNs, the student will then carry out targeted experimental validation of two to three of the strongest convergent candidates using CRISPR interference and activation (CRISPRi/a) in human stem cell-derived striatal neurons. This uses gene-regulation lines and quantitative readouts of neuronal identity, subtype balance and maturation already established in the group.
The student will gain a distinctive combination of skills spanning statistical and single-cell genomics, gene-set enrichment, cohort-based phenotype analysis and reproducible computational pipelines, together with hands-on human stem cell and CRISPRi/a experience. They will be supervised jointly by Dr Marija Fjodorova (stem cell modelling of the striatum) and Dr Elliott Rees (psychiatric genetics and large-scale cohort analysis), within Cardiff University's world-leading environment for psychiatric genetics and translational neuroscience, with access to advanced computing, single-cell atlases and established iPSC and CRISPRi/a platforms.
The expected outcomes are a reproducible, cross-disorder framework identifying convergent striatal mechanisms of psychiatric risk, evidence for biologically meaningful patient strata, and a validated set of MSN readouts, outputs that reframe these disorders around shared, treatment-relevant biology rather than diagnostic labels. By defining mechanisms shared across genetically distinct conditions, the work points towards convergent rather than gene-by-gene therapeutic routes. The project would suit a student with quantitative aptitude and an interest in psychiatric genetics, genomics or computational biology, who is also keen to gain laboratory experience in human stem cell models.
Entry Requirements
Applicants should possess a minimum of an Upper Second Class Honours degree, Master's degree, or equivalent in a relevant subject (as detailed above).
How to Apply
This studentship has a start date of October 2027
In order to be considered you must submit a formal application via Cardiff University's online application service.
There is a box at the top right of the page labelled 'Apply', please ensure you select the correct 'Qualification' (Doctor of Philosophy), the correct 'Mode of Study' (Full Time) and the correct 'Start Date' (October 2027). This will take you to the application portal.
In order to be considered candidates must submit the following information:
- CV
- Supporting Statement
- Official Qualification Certificates and/or Transcripts
- Proof of English Language (if applicable)
- References (x2)
Funding Notes
THIS PROJECT IS ONLY OPEN TO CHINA SCHOLARSHIP COUNCIL (CSC) APPLICANTS
For more information please visit - https://www.cardiff.ac.uk/study/international/funding-and-fees/international-scholarships/china-scholarship-council
