Technologies for Mapping the Extracellular Interactome

在此输入文本，它是应用程序的新摘要信息。本节时应 不超过30行文字。 定义生物体中存在的分子相互作用和网络的整个集合 (i.e.,互动组）是理解功能，动力学和逻辑的基础 复杂的细胞系统大规模的努力，包括酵母双杂交方法和 亲和-质谱法已经开始定义真核相互作用物组的大部分。 虽然这些方法已被证明对评估细胞质相互作用是有效的，但它们 不足以定义涉及1/3的人类蛋白质组的相互作用， 分泌蛋白和整合膜蛋白的胞外域。这些蛋白质及其 相互作用对细胞和多细胞过程至关重要，因为它们检测发育， 形态发生和环境线索是正常生理和病理的核心。 这些受体：配体复合物还提供了作为治疗靶点和用于治疗的巨大前景。 治疗自身免疫性疾病、感染性疾病和 恶性肿瘤。目前还没有平台来支持这些细胞外的发现， 交互. 为了应对这一挑战，我们最近为两个不同的 高通量平台，用于绘制“外相互作用组”， 由分泌蛋白和细胞表面蛋白形成。这些努力利用了一个多学科的团队， 由蛋白质化学家、自动化专家和生物学家组成， 利用尖端细胞微阵列和流式细胞术的蛋白质表达/呈递策略 技术.这些平台的优化和实施有望 通过揭示细胞外相互作用和网络，产生新的 对正常生理、疾病和治疗策略的见解。我们的定位是 在评估界定外相互作用组的可行性方面取得了重大进展。连同 大量的细胞质相互作用正在积累，这些研究将提供 重要的见解，全方位的分子电路，整合多个不同的 将信号转化为细胞和多细胞功能。

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Defining the entire ensemble of molecular interactions and networks present in an organism (i.e., the Interactome) is essential for understanding the function, dynamics and logic underlying complex cellular systems. Large-scale efforts, involving both yeast-two-hybrid approaches and affinity-mass spectrometry, have begun to define large portions of the eukaryotic Interactome. While these approaches have proven effective for evaluating cytoplasmic interactions, they are inadequate for defining the interactions involving the 1/3 of the human proteome represented by secreted proteins and the ectodomains of integral membrane proteins. These proteins and their interactions are vital to cellular and multi-cellular processes as they detect the developmental, morphogenetic and environmental cues that are central to normal physiology and pathology. These receptor:ligand complexes also offer enormous promise as therapeutic targets and for the development of biologics to treat autoimmune diseases, infectious diseases and malignancies. At present there exists no platform to support the discovery of these extracellular interactions. To address this challenge, we have recently established strong proof-of-concept for two distinct high-throughput platforms for mapping of the “Ecto-Interactome”, the entire set of interactions formed by secreted and cell surface proteins. These efforts exploit a multi-disciplinary team, composed of protein chemists, automation specialists and biologists, which is merging multiple protein expression/presentation strategies with cutting-edge cell microarray and flow cytometry technologies. The optimization and implementation of these platforms promises to have transformative impact by revealing extracellular interactions and networks that yield novel insights into normal physiology, disease and therapeutic strategies. We are positioned to make significant progress in assessing the feasibility of defining the Ecto-Interactome. Together with the considerable body of cytoplasmic interactions that is accruing, these studies will provide important insights into the full range of molecular circuitry that integrates multiple disparate signals into cellular and multi-cellular function.