Protein complex inter-connections in Drosophila

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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.