Exploring the early genetic origins of schizophrenia at the cellular level

Schizophrenia is a severe psychiatric disorder affecting ~1% of the population. Recent large-scale genomic studies have identified hundreds of schizophrenia genetic risk loci, paving the way for much-needed biological insights into the condition. Our own research and that of others has indicated that many of these genetic risk variants operate in utero, substantiating long-held neurodevelopmental theories of the disorder. However, the prenatal brain regions and cell types through which these genetic risk variants operate remain unclear. This PhD project will build upon a current MRC project grant to lead supervisor Bray which is using single-cell sequencing to assess gene expression and its regulation in the constituent cell types of the human foetal brain. The student will combine use of this cutting-edge wet-lab technology with the latest genetic data for schizophrenia (available through the host MRC Centre for Neuropsychiatric Genetics & Genomics) to identify cell types of the prenatal brain mediating genetic risk for the disorder. Through the two host centres, they will be trained in both state-of-the-art laboratory techniques for profiling cellular gene expression and sophisticated biostatistical methods for its analysis and integration with large-scale genetic data. The student will additionally benefit from use of related epigenomic and transcriptomic data generated by the Cardiff and Exeter supervisors' groups (from both foetal and adult human brain) as well as from established international collaborations (e.g. with the Psychiatric Genomics Consortium, PsychENCODE). The impact of the student's research will be maximised through their regular attendance at international conferences (e.g. World Congress on Psychiatric Genetics, Society for Neuroscience), publication in leading journals and dissemination through data-sharing repositories.