CAREER: Analysis of the Coiled-coil Interactome

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The research objective of this project is to use computational methods to link the molecular properties of protein-protein interactions to their broader biological roles in the genome. The project aims to demonstrate that a structural understanding of protein interaction motifs can contribute to the interpretation of high-throughput studies of protein-protein interactions, and can lead to specific and testable hypotheses about protein associations and function. The work tests this idea using the alpha-helical coiled coil, a common and important interaction motif, as an example. The specific research objectives are: (1) To build a database containing the coiled-coil sequences from numerous genomes, along with the properties of the coiled coils, the functions of the proteins, and other annotation; (2) To combine these data with structural considerations to validate high-throughput protein-protein interaction studies and to predict coiled coil-mediated interactions; and (3) To experimentally verify putative coiled coil mediated interactions predicted to have important biological roles.Broader Impacts: Dr. Keating's research and teaching at MIT are carried out in the emerging areas of computational and systems biology. These fields will have a tremendous impact on science and society in the next several decades. The sequencing of the human genome, as well as that of important pathogens, crops and scientific model organisms, has provided an opportunity for fundamentally new kinds of research combining biology, computer science, math, engineering and other quantitative fields. This interdisciplinary approach promises a deeper understanding of biology, as well as breakthroughs in biotechnology and molecular therapeutics. It is critically important to develop foundational methods for this kind of science and to provide appropriate training for undergraduate and graduate students who want to work in this area. The research described above, coupled with Dr. Keating's active role in CSBi, MIT's educational, research and outreach initiative in Computational and Systems Biology, will bring us closer to these goals.