It is now clear that genetics alone cannot explain the majority of the observed phenotypic traits and cellular response to perturbation. One of the fundamental questions in aging biology is to understand the complexity with which cellular systems respond to stimuli and stress. Proteins perform nearly all the work of the cell. It is therefore important to measure directly the effects of aging on the proteome itself, as opposed to an indirect molecular phenotype like the transcriptome. The direct analysis of proteins, their modifications, and their flux has the potential to greatly enhance our ability to identify and understand the functional pathways that underlie the biology of aging. A challenge to this task has been that the field of MS-based proteomics has long suffered from a reputation of difficulty in reproducing experimental measurements. This irreproducibility has been primarily due to the semi-stochastic way in which shotgun proteomics measurements have been made. To address these issues, the MacCoss and Villen labs has been at the forefront of developing technologies to perform large-scale targeted proteomics assays that generate near complete data matrices, accurate quantitation, and high reproducibility ? even across multiple laboratories. The primary goal of Core C is to apply these improved methods to studies of aging, to obtain accurate quantitative measurements of peptides from samples provided by its users, and to aid geroscience researchers in linking these high-dimensional data to biologically meaningful outcomes. In addition, the Core will develop and apply new assays especially suited to aging. This Core will work closely with Core D (Metabolite Phenotypes of Aging), which will share some of the same facilities, and with Core E (Invertebrate Longevity and Healthspan) and Core F (Artificial Intelligence and Bioinformatics). The resources offered here include methods that can be applied to a wide range of species, including humans. Core C will also play a key role in collaborative efforts between the University of Washington Nathan Shock Center (NSC) and other NSCs throughout the country. Core C will devote considerable resources to technology and software development, ensuring that we are constantly pushing the scientific boundaries in this field. In the long term, Core C will help to make comprehensive, age-specific protein phenotypes an essential and invaluable component of any study of aging phenotypes. The core will impact on biogerontology at the broadest level, enabling our collaborators to identify new mechanistic pathways linking genes with aging, including pathways that have the potential to reveal new drugs to target aging. Moreover, these capabilities will lead to resources of value not just to collaborating Nathan Shock Centers but to others in the biogerontology community, and ultimately, to all researchers interested in the proteomic foundations of biomedically relevant problems.
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