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超高通量图谱 摘要 该催化剂项目旨在通过以下方式消除了解糖尿病及其并发症的主要瓶颈 开发在基因组上绘制疾病相关细胞中不同分子相互作用图的技术 比例。这些拟议的技术，统称为PRACI(蛋白质、RNA和染色质相互作用)，将 使典型的研究实验室能够绘制全基因组的蛋白质-蛋白质、RNA-蛋白质、RNA-RNA和RNA- DNA/染色质相互作用网络在1个月内从给定的细胞类型。PRACI使典型实验室能够 比较健康和疾病状态之间的分子相互作用网络。没有PRACI，全基因组 绘制疾病相关细胞类型的单一类型相互作用的图谱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图，使用 以高血糖和慢性炎症诱导的血管内皮细胞不可逆性改变为实验床 系统。我预计将揭示多尺度分子网络的哪些组件负责 功能失调的内皮细胞基因表达持续失调。这样的信息将导致新的 考虑到内皮功能障碍对糖尿病创面的作用，糖尿病创面愈合的前景 以及血管系统的相对可获得性。我预计，这些技术及其实现的发现 将有助于并激励糖尿病、内分泌学和新陈代谢研究的变革性变化 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.