Spatial and Temporal Genomics
Cells in complex mammalian tissues, such as the brain, are spatially organized and dynamic, yet almost all genomic tools lack temporal and spatial resolution. Our laboratory, at the Broad institute, sets out to build a set of tools which will bridge single-cell genomics with space and time – to enable discoveries of where cell types are localized within intact tissues, when relevant transcriptional modules are active. To do this, we are developing novel technologies at the intersection of microscopy, genomics, synthetic biology, and computational analysis. We are applying these tools to learn organizational principles governing development, and cellular mechanisms of disorganization during injury and disease.
Current approaches for transcriptomic analysis involve grinding up or dissociating the tissue, while in situ hybridization (ISH) approaches are often limited to profiling one transcript at a time. However, to map the spatial heterogeneity of complex tissues requires us to bridge the divide between spatial and molecular resolution. We are developing new tools at the intersection of microscopy and genomics. These include Slide-seq, an approach which enables high resolution profiling of the transcriptome using spatially barcoded bead arrays, as well highly multiplex microscopy methods. We are interested in using these approaches to understand tissue organization with respect to communication between cells and cellular networks in development and pathology.
The genome is 3 billion bases of DNA packaged into a 10-micron nucleus. The 3D organization of the genome, and the associated protein, RNAs, and cellular structures, regulate gene expression and cellular function. We are developing new genomic technologies which enable simultaneous sequencing and imaging of genomes in intact samples, uncovering genome-wide organizing principles across length scales in cells.