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Our group studies the large-scale organization of proteins, essentially trying to reconstruct the 'wiring diagrams' of cells by learning how all of the proteins encoded by a genome are associated into functional pathways, systems, and networks. We are interested both in discovering the functions of the proteins as well as in learning the underlying organizational principles of the networks. The work is evenly split between computational and experimental approaches, with the latter tending to be high-throughput functional genomics and proteomics approaches for studying thousands of genes/proteins in parallel.

Bioinformatics of protein function and interactions

We've discovered a number of features of genomes that allow us to predict functions for proteins that have never been experimentally characterized. Using these techniques and information from over 30 fully sequenced genomes, we were able to calculate the first genome-wide predictions of protein function, finding very preliminary function for over half the 2,500 uncharacterized genes of yeast. Now, with over 80 genomes in hand, we're extending these techniques, as well as asking fundamental questions about the evolution of protein interactions and the evolution of genomes.

Proteomics: High-throughput protein expression and interaction profiling

From our work and others, it is apparent that proteins in the cell participate in extended protein interaction networks involving thousands of proteins. In the near term, we hope to begin developing protein interaction microarrays to measure interactions between all proteins encoded by a cell. In the long term, we would like to build a catalog of protein, mRNA and metabolite expression from cells grown under many different conditions, forming a quantitative picture of these molecular events inside cells. We expect that data of these sorts will put us on the road to developing predictive, rather than descriptive, theories of biology.