From Risk Genes to Biomarkers in Schizophrenia: Striatal-Immune Signatures for Patient Stratification

About the Project

This is a Self-Funded/Sponsored PhD opportunity.

FUNDING REQUIRED:

• Full UK/EU or International Tuition Fees
• UK Living Expenses
• Bench Fees (£9,000 total)

Open to all students of any nationality without restrictions (UK/EU and International)

Description:

Schizophrenia and related psychotic conditions are clinically heterogeneous, and progress is limited by the lack of validated biomarkers that reflect underlying biology and enable patient stratification. While most genetic-to-biology studies have focused on cortical circuitry, increasing evidence implicates the basal ganglia – particularly the striatum – in psychosis risk and symptom expression (e.g., reward, habit learning, and dopaminergic signalling). Striatal neuronal populations, including medium spiny neurons and key circuit partners, have therefore emerged as a promising but still understudied substrate for schizophrenia biology. In parallel, immune and complement pathways, and microglia-mediated synaptic pruning, are increasingly implicated in schizophrenia pathophysiology.

This PhD will develop and validate novel biomarker candidates by linking schizophrenia genetic liability to cell-type-specific molecular and functional signatures across basal ganglia neuronal populations and neuroimmune mechanisms. The student will:

(i) curate schizophrenia risk signals from major resources (e.g., Psychiatric Genomics Consortium outputs and related datasets), partitioning burden by variant class;

(ii) map cell-type enrichment using brain-wide single-cell atlases with established statistical genetics tools (e.g., MAGMA and regression-based enrichment);

(iii) test whether cell-type-weighted risk signatures predict basal ganglia- and immune-relevant traits in UK Biobank and available cohorts, using regularised regression and clustering (with covariate control) to define biologically meaningful strata;

(iv) perform targeted experimental validation of 2-3 top genes/pathways using CRISPR interference/activation (CRISPRi/a) perturbations in stem cell models, prioritising striatal neurons alongside glial/immune cells. Quantitative readouts will include maturation and synaptic/neurite phenotypes, complement/cytokine outputs, and functional activity signatures.

The aim of this PhD is to develop a reproducible genetics-anchored biomarker pipeline, validate striatal-immune risk signatures, and generate a shortlist of mechanistically supported translational cellular readouts for schizophrenia stratification and future therapeutic development.

Entry Requirements

You will hold or expect to achieve a First or Upper Second Class degree in biomedical science, biochemistry, cell biology or a related subject. As this is a training doctorate, previous research experience is not essential.

Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS).

How to Apply

This studentship has a start date of October 2026. 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 2026). This will take you to the application portal.

In order to be considered candidates must submit the following information:

• Supporting statement
• CV
• Qualification certificates
• References x 2
• Proof of English language (if applicable)