Exploring the early genetic origins of schizophrenia at the cellular level

在细胞水平探索精神分裂症的早期遗传起源

• 批准号: 2750466
• 金额: --
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2750466
• 关键词: Exploring; early; genetic; origins; schizophrenia

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.

精神分裂症是一种严重的精神疾病，影响约 1% 的人口。最近的大规模基因组研究已经确定了数百个精神分裂症遗传风险位点，为对该疾病的急需生物学见解铺平了道路。我们自己和其他人的研究表明，许多遗传风险变异在子宫内发挥作用，证实了长期以来关于该疾病的神经发育理论。然而，这些遗传风险变异发挥作用的产前大脑区域和细胞类型仍不清楚。该博士项目将建立在目前向首席导师 Bray 提供的 MRC 项目资助的基础上，该项目正在使用单细胞测序来评估基因表达及其在人类胎儿大脑组成细胞类型中的调节。学生将利用这种尖端的湿实验室技术与最新的精神分裂症遗传数据（可通过主办的 MRC 神经精神遗传学和基因组学中心获得）来识别介导该疾病遗传风险的产前大脑细胞类型。通过这两个主办中心，他们将接受最先进的实验室技术（用于分析细胞基因表达）和复杂的生物统计方法（用于分析和与大规模遗传数据整合）的培训。此外，学生还将受益于使用卡迪夫和埃克塞特督导小组（来自胎儿和成人大脑）以及已建立的国际合作（例如与精神病学基因组学联盟、PsychENCODE）生成的相关表观基因组和转录组数据。通过定期参加国际会议（例如世界精神病遗传学大会、神经科学学会）、在领先期刊上发表文章以及通过数据共享存储库进行传播，学生研究的影响将得到最大化。