This proposal requests funding to purchase a Thermo Fisher Scientific Orbitrap Elite mass spectrometer to support new proteomics efforts in the Epigenetics Program in the Perelman School of Medicine at the University of Pennsylvania. The Epigenetics Program was recently established in 2009 to promote and develop basic research in chromatin biology and epigenetics, and to organize and encourage collaborations between basic and clinical scientists. Among several objectives of the Epigenetics Program is the establishment of core research technologies which currently include Functional Genomics, Robotics and High-throughput qPCR, Chromatin and Nucleosomes, and Computational Epigenetics. The newest core being established by the Epigenetics Program is the Proteomics Resource core where the Orbitrap Elite instrument will be housed next to the laboratory of the PI to ensure maximum usage and routine maintenance. Currently, there are over 60 NIH-funded faculty members in the Epigenetics Program spanning 7 different Philadelphia area universities, and this instrument will initially support the research of 11 major and 7 minor users with over 40 active NIH funded grants. The projects supported by this instrument include a vast depth and breadth of biological areas and proteomics experimentation geared at charactering protein abundance and post-translational modification (PTM) changes. These studies include examining the link between metabolism and gene regulation, chromatin modifications involved in aging, pluripotent stem cell signaling pathways, altered lysine methyltransferase activity in cancer, interrogating the crosstalk between cellular and chromatin networks and obtaining single gene protein profiles, just to name a few. Quantitative proteomic experiments afforded by this new instrument for these projects include Top and Middle Down analyses of histone and non-histone combinatorial PTM codes, pulse stable isotope labeling of amino acids in cell culture (pulse SILAC) for determining PTM-specific turnover/dynamics, global proteome and phosphoproteome scale quantification by SILAC and tandem mass tagging (TMT), and H/D exchange structural experiments on nucleosomes containing specialized protein variants, among others. The different types of large-scale quantitative proteomics experiments described in this proposal either have never been performed or are not routinely performed on the Penn campus due to lack of appropriate instrumentation or capabilities. The studies that will be enabled by this instrument are directly related to human health as epigenetic mechanisms have been shown to play intricate roles in many processes such as neurological and immunological disorders, and diseases such as cancer.

Public Health Relevance

On-site access to an Orbitrap Elite hybrid mass spectrometer will enable scientists in the Perelman School of Medicine at the University of Pennsylvania to conduct cutting-edge quantitative proteomics research efforts directed at various epigenetic targets. The requested instrument has vastly improved resolution, accuracy and increased data collection rates compared to all previous generations. The research to be supported by this instrument spans a wide variety of biomedical research including cancer, regenerative medicine, aging, cardiovascular disorders and women's health.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-BCMB-D (30))
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Birken, Steven
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University of Pennsylvania
Schools of Medicine
United States
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