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

健康和疾病中蛋白质、RNA和染色质相互作用的极高通量图谱 摘要 该催化剂项目旨在消除理解糖尿病及其并发症的主要瓶颈， 开发技术，在基因组上绘制疾病相关细胞中的各种分子相互作用， 规模这些拟议中的技术，统称为PRACI（蛋白质，RNA和染色质相互作用），将 使一个典型的研究实验室能够绘制全基因组蛋白质-蛋白质、RNA-蛋白质、RNA-RNA和RNA- 在1个月的时间内从给定的细胞类型的DNA/染色质相互作用网络。PRACI使典型的实验室能够 比较健康和疾病状态之间的分子相互作用网络。如果没有PRACI， 从疾病相关的细胞类型绘制甚至单一类型的相互作用仍然是一项艰巨的任务。 我将系统地绘制与糖尿病相关血管并发症相关的分子相互作用组变化， 以高血糖和慢性炎症引起的血管内皮细胞不可逆性改变为实验平台 系统我期望揭示多尺度分子网络的哪些组成部分负责 功能障碍的内皮细胞中基因表达的持续失调。这些信息将导致新的 鉴于内皮功能障碍对糖尿病伤口的既定作用， 和脉管系统的相对可及性。我预计这些技术和它们带来的发现 将有助于并激发糖尿病，内分泌学和代谢研究的变革 疾病

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.