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Mr Simon

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Mr Simon
Jeremy Zucker: Statement of Purpose | It was about 10:30 at night, and except for a small desk lamp and the glow from my computer monitor, it was dark. The genome of the photosynthetic bacteria Prochloroccocus marinus, responsible for providing nearly 40% of the world's energy needs, had just been sequenced. I loaded the draft version of the genbank file into my software pipeline I spent the last two years developing. Minutes later, a genome-scale reconstruction of the P. marinus metabolism appeared on my screen. In that moment, I knew I was the first person to view the entire metabolism of this cyanobacteria. I remember the chills going down my spine, the palpitation of my heart, and the rush that comes only from breathing the rarified air of discovery.The original motivation for this research came from a paper written in 1999 called "Towards Metabolic Phenomics: An analysis of Genomics using Flux Balances". In this paper, Schilling, Edwards and Palsson noted that with the rapid completion of bacterial genomes, ORFeomes and proteomes, we are therefore at the brink of having a complete 'part catalog' of many organisms. Based on that observation, they predicted our ability to understand the complex relationship between genotype and phenotype will be limited "not by the data, but by our tools to analyze and interpret this data." Finally, they proposed a bioinformatics pipeline to automatically generate metabolic flux models from an annotated genome, arguing that a rigorous constraint-based analysis of these models would enable us to iteratively refine our knowledge.Inspired by this argument, I implementated their proposal for the Church Lab at Harvard Medical School, enabling us to generate experimentally verifiable flux predictions based on different hypotheses for bacterial growth. This work is described in a paper we published with the ungainly title of "From annotated genomes to metabolic flux models and kinetic parameter fitting." Based on this experience, I

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