The Proteomics Core will target pathological processes associated with protein structures in aging systems. The emphasis will be on using mass spectrometry-based technologies and chemical methods to identify posttranslational protein modifications, such as phosphorylation or oxidative modification, which appear to play important roles in aging and age-related diseases. The Core will also carry out experiments involving high-throughput protein identification and protein expression changes, and defining protein-protein interaction networks in complex biological systems. These activities will extend the Buck Institute's role as a regional center of expertise in proteomics, particularly in applications to posttranslational modifications and protein-protein complexes. New methods have been developed by the Core for determining the proteomes of whole organelles (e.g., mitochondria), protein phosphorylation, cysteine redox status, and changes in protein structure using chemical crosslinking strategies (MS3D). The continued development and application of these methodologies will further enhance the Buck Institute's ability to serve as a regional or national resource for proteomics in aging systems. A key feature of our proposal is the exploitation of a new quadrupole linear ion trap mass spectrometer for these proteomic applications. The 4000 QTRAP hybrid triple quadrupole-linear ion trap instrument will provide high sensitivity, enhanced resolution scanning and enhanced product ion scanning when operated in the linear ion trap mode, while also retaining all conventional triple quadrupole scanning modes, such as multiple reaction monitoring, neutral loss and precursor ion scanning. Together with existing resources and staff at the Institute, the proposed 'Proteomics in Aging Facility' will greatly enhance our efforts at detailing the molecular events in the proteome that underlie the complex aging process in cells, tissues and organisms, as well as for age-related diseases, such as Alzheimer's disease.
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