Whole Brain Single Cell-Omics for Understanding Brain Function and Dysfunction
A mammalian brain is staggeringly complex. It consists of billions of neurons forming thousands of specific connections with other neurons. Moreover, each individual neuron belongs to one of thousands of genetically distinct populations. Even within the same nominal class of neurons, individual cells show clear heterogeneity. In studying how genes and environmental factors affect function and dysfunction of such a complex system, technologies that enable rapid extraction of brain-wide anatomical connectivity (connectome) as well as molecular details (transcriptome, proteome, and metabolome) from the same brain at single cell resolution, would have the potential to radically accelerate the rate of discovery. We develop and apply such transformative techniques to identify neuronal circuits, subcellular structures, genes and molecules that are abnormal in the diseased brain. Based on these finding, we utilize animal models and postmortem human brain tissue to understand the core mechanisms through which genes and environmental factors cause brain dysfunction. We hope our research lead us to identify new therapeutic targets and guide the development of new therapeutic strategies.