Sites of active gene regulation in the developing human brain and their role in neuropsychiatric disorders

Human brain development is orchestrated by dynamic changes in gene expression. In recent years, there have been major advances in methods for studying regions of the genome that regulate this process. However, data from the developing human brain are extremely limited. Through the MRC / Wellcome Trust-funded Human Developmental Biology Resource, we have collected brain tissue from > 150 human foetal donors. The student will use these samples to identify active regulatory regions throughout the genome at different developmental stages using ATAC-Seq (Buenrostro et al, Nature Methods 2013), a cutting-edge laboratory technique for identifying regions of open chromatin that are accessible to the transcription factors that promote gene expression. The student will be trained in sophisticated bioinformatics / statistical techniques for analysis of these data and their integration with other genome-wide data from the same samples (genotyping, DNA methylation, RNA sequencing). As many of the genetic risk variants for neuropsychiatric disorders (e.g. schizophrenia, autism) are hypothesised to operate during early brain development, the student will also relate their findings to genetic data generated by the primary host department (the MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff) through large-scale genomic studies of these disorders (e.g. Schizophrenia working group of the Psychiatric Genomics Consortium, Nature Genetics 2014).