Protein complex inter-connections in Drosophila

果蝇中蛋白质复合物的相互连接

• 批准号: 8633470
• 负责人: SPYRIDON ARTAVANIS-TSAKONAS
• 金额: $ 21.19万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-08 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8633470
• 关键词: Affect; Affinity Chromatography; Architecture; Cell physiology; Cells; Complex; Core Protein; Coupled; Development; Drosophila genus; Gene Mutation; Genes; Genetic; Genomics; Hemocytes; Image; Imaging Techniques; Individual; Life; Maps; Mass Spectrum Analysis; Mediating; Molecular; Physiological; Property; Protein-Protein Interaction Map; Proteins; RNA Interference; Staging; System; Technology; Time; Tissues; Transgenic Organisms; blastomere structure; in vivo; insight; member; network architecture; novel; protein complex; public health relevance

DESCRIPTION (provided by applicant): Proteins govern cell physiology and development and rarely act alone, but rather as members of complexes that define interconnected functional units. Determination of the particulars of such a network is an essential step in understanding the cell as an integrated system. Recently we defined a Drosophila Protein interaction Map (DPiM) using a high- throughput co-affinity purification platform coupled to mass spectrometry analysis (coAP-MS) [1]. The analysis of haemocyte-like embryonic cells revealed the existence of a protein interaction network encompassing 556 complexes, which include the products of several hundred previously unannotated genes. The existence of the map allows us, for the first time, to ask questions regarding how intra-complex protein interactions as well as inter-complex interactions affect the overall architecture of the network. Such relationships will provide insighs into how functional cellular units, defined by the existence of specific protein complexes, are integrated within the cell. In this exploratory proposal we wish to examine the dynamic properties of the protein network by examining the interconnectedness of complexes defined by the DPiM as well as probing the existence, distribution and composition of a select subset of complexes when confronted with diverse developmental contexts in vivo. The proposed analysis has both basic and translational value, given that it will open the way to probe complex, system-wide interactions under different physiological conditions imposed by genetic mutation or pharmacological manipulation.

描述（由申请人提供）：蛋白质控制细胞生理和发育，很少单独起作用，而是作为定义相互连接的功能单元的复合物的成员。确定这种网络的细节是理解细胞作为一个综合系统的必要步骤。最近，我们使用高通量共亲和纯化平台耦合质谱分析（coAP-MS）[1]定义了果蝇蛋白相互作用图谱（DPiM）。对红细胞样胚胎细胞的分析揭示了包含556个复合物的蛋白质相互作用网络的存在，其中包括数百个以前未注释的基因的产物。该图谱的存在使我们第一次能够提出有关复合体内部蛋白质相互作用以及复合体之间相互作用如何影响网络整体结构的问题。这种关系将提供对功能性细胞单位（由特定蛋白质复合物的存在所定义）如何在细胞内整合的见解。在这个探索性的提议中，我们希望通过检查由DPiM定义的复合物的相互联系来检查蛋白质网络的动态特性，以及在体内面对不同发育环境时探测一组选择的复合物的存在、分布和组成。所提出的分析具有基础和转化价值，因为它将为探索基因突变或药理学操作所施加的不同生理条件下复杂的全系统相互作用开辟道路。