A metabolism-centric proteomic map on the genomic scale: enabling functional annotation of the unknown genome

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We will create a genome-spanning functional proteomic map of the model eukaryote Saccharomyces cerevisiae, and use it to dissect the compendium of metabolism-regulating genes, and to annotate yet unknown genes on the basis of their proteomic footprint. This map will be created by systematically recording SWATH-MS based proteome profiles from 4800 yeast single gene knock-out strains, representing the fraction of gene deletions viable in the absence of rich nutrient supplementation, chosen to enable growth that is informative about biosynthetic metabolism. This unique large-scale project will be facilitated by an academia/industry partnership to establish a high-throughput variant of SWATH-MS technology invented by the collaborating laboratory of Ruedi Aebersold, and be capable to process thousands of samples in a proteomic experiment by combining microflow-chromatography, advanced ionisation techniques, and data independent acquisition.

This is an academia-industry collaboration with direct impact. The biotechnological industry will obtain the information about which gene has to be manipulated in the genome to affect 80% of enzymes and can use this information to develop new production strains, save money by improving existing production cycles for instance to reduce greenhouse gas emissions. The mass spectrometry manufacturing industry will get access to a workflow that allows implementing proteomics technology in industrial scale projects, including diagnostics and environmental analytics, and improve access to a new market for proteomics. Enabling proteomics for the large scale will directly benefit society, that depends on diagnostics in medicine and environmental analytics for food production and marketing. Finally, the results clearly impact basic science, as we will substantially improve the annotation of ~2000 budding yeast genes that are functionally yet uncharacterized.