Extremely high-throughput mapping of protein, RNA, and chromatin interactions in health and disease

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Extremely high-throughput mapping of protein, RNA, and chromatin interactions in health and disease Abstract This Catalyst project aims to removing a major bottleneck in understanding diabetes and its complications, by developing the technologies to map diverse molecular interactions in the disease-relevant cells at the genomic scale. These proposed technologies, collectively called PRACI (Protein, RNA, and chromatin interactions), will enable a typical research lab to map genome-wide protein-protein, RNA-protein, RNA-RNA, and RNA- DNA/chromatin interaction networks from a given cell type within 1 months’ time. PRACI enables typical labs to compare molecular interaction networks between health and disease states. Without PRACI, genome-wide mapping of even a single type of interactions from a disease-relevant cell type remains a formidable task. I will systematically map molecular interactome changes related to diabetes related vascular complications, using hyperglycemia and chronic inflammation-induced irreversible alterations vascular endothelial cells as a testbed system. I anticipate to reveal which components of the multiscale molecular networks are responsible for the sustained dysregulation of gene expression in dysfunctional endothelial cells. Such information will lead to new perspectives to diabetic wound healing, given the established roles of endothelial dysfunction to diabetic wounds and the relative accessibility of vasculature. I anticipate that these technologies and their enabled discoveries will contribute to and inspire transformative changes in the study of Diabetes, Endocrinology, and Metabolic Diseases.