PROJECT SUMMARY The advent of genome technologies for interrogating gene expression has irreversibly changed the scale at which scientists investigate biological problems. More specifically, large-scale gene expression sequencing technologies have allowed us to glean insights into biology and disease pathogenesis at unprecedented pace. However, RNA levels are only one piece of a highly complex biological puzzle: genes are the starting point of the cellular regulatory process, while metabolites are often the end products and the ultimate biological effector molecules. There are many layers of regulation post-expression that fine-tune the biological system in the path from gene to protein to metabolite. Recognizing the central role of proteins and their post-translational modifications (PTMs) in this process, the National Center for Quantitative Biology of Complex Systems was founded to provide large-scale quantitative data for these molecules. Our Biotechnology Research Resource aims to accelerate the pace, depth, and accuracy of quantifying the proteome, metabolome, and lipidome. Driven by the needs of biomedical researchers, our mission is to develop technologies that provide rapid access to the most comprehensive and accurate reporters of the biological state. Specifically we will (1) extend and ultimately culminate our work to enable comprehensive biomolecule characterization; (2) develop and conclude our work enabling highly multiplexed proteome quantification and (3) break ground on the development of the novel chromatographic and mass spectrometry platform for wholly integrated multi-omic analysis. We shall develop these technologies in the context of several high impact driving biomedical research projects that require the new technological advancements for success and that can serve as technology testbeds. These driving projects comprise two central themes. First, responding to the demands of biomedical researchers to explore the roles of emergent and yet poorly understood biomolecules and their PTMs, we will target projects concerned with new, metabolite-derived post-translational modifications. Second, we have come to appreciate that in addition to protein measurements our collaborators require new technologies to identify and quantify metabolites and lipids to fully understand their biological systems of interest and we will work with a host of projects that allow us to test and refine technologies for the large-scale systems and multi-omics analyses to explore physiology and metabolism. Finally, we propose a multi-faceted approach to dissemination, training, and collaboration, with the ultimate aim of ensuring the sustained impact of our technology. All of our technologies are designed to be sustainable, and we have created both systematic and informal mechanisms to deliver our knowledge and innovations to the scientific community.

PROJECT NARRATIVE The National Center for Quantitative Biology of Complex Systems develops novel technologies that accelerate the pace and depth of protein, lipid, and metabolite analysis. These molecules, and their interactions, regulate the complex cellular processes underlying many devastating diseases. Specifically, the technologies developed in this Resource are being used to advance our understanding of many human conditions including diabetes, Alzheimer’s disease, cancer, and heart disease, among others.