Neurodevelopment and aging
Human brain development is an intricate process involving the dynamic orchestration of gene expression. The precise temporal regulation of transcriptional processes is necessary for the correct development of structural and functional complexity in the brain. We are undertaking a series of studies to systematically examine epigenomic and transcriptomic trajectories across the life-course, looking at genomic regulation from fetal development to old age. For example, we recently published a genome-wide analysis of DNA methylation in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 days post-conception. Data from this project is available as a searchable web-tool.
Functional genomic annotation of the human brain
Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the genomic differences that occur between functionally distinct areas of the human brain. We are characterizing intra- and inter-individual epigenomic and transcriptomic variation across multiple regions of the brain from multiple donors. A recent publication from our group details the first results of this study.
Single-cell genomics in the human brain
Individual cells exhibit substantial genetic, epigenetic and transcriptomic differences, even when derived from an apparently homogenous population. This cellular heterogeneity may have important functional consequences relevant to health and disease. Despite this, it is largely overlooked and completely hidden from standard genomic profiling methods which can only detect aggregate values (e.g. of gene expression) derived from profiling bulk tissue or large populations of cells. We are using the most recent advances in single-cell profiling technology (e.g. 10x Genomics Single-Cell RNA-Seq and ATAC-Seq, Fluidigm C1 microfluidic system) to profile gene expression and the epigenetic landscape of individual cells in the brain. In doing so we hope to get a better understanding of the role of cell-type specific changes in gene-expression or chromatin accessibility in a range of diseases.