Stanford University is home to some of the world's most progressive biological and medical research. Proteomics as a research application, providing insightful answers to fundamental biological questions, is now a prerequisite. One of the cornerstones of proteomics, if not the foundation, is mass spectrometry. The technological development of mass spectrometric instrumentation in parallel with computational resources over the past five years has given rise to the complete identification and quantification of the yeast proteome, complete post-translational mapping of human histones and isoforms thereof, as well as the ability to map signaling events (phosphoproteome) as a response to stimulation on a global proteomic scale. These profound findings are inextricably linked to the capabilities of modern instrumentation. This proposal seeks funds to assist in the purchase of a new LTQ Orbitrap XL ETD mass spectrometer. The Orbitrap will be professionally operated and maintained in Stanford's mass spectrometry core facility, Stanford University Mass Spectrometry (SUMS). SUMS'current 1-year user base includes 245 students, faculty, and staff in 80 research groups from 26 departments distributed across the schools of Medicine (60%), Humanities and Sciences (30%), and Engineering (10%). The capabilities of the Orbitrap mass spectrometer are proven, and the technical expertise to operate the instrumentation and translate the resulting data into biologically meaningful results is already present in SUMS. The addition of the Orbitrap would make research projects that are now in high demand viable. Amongst many other applications, the high mass accuracy and sensitivity of the instrument would enable quantitative proteomic studies on cancer cells, stem cells, and fetal mouse serum. The capabilities of ETD would be utilized in phosphoproteomic characterization of proteins involved in plant cell signaling and tumorgenesis. In addition, the instrumentation would enable top-down and middle-down characterization of proteins critical to viral progression. The research projects of seven major users, as described in the proposal, are highly relevant to human health and disease, with particular impacts on viral and bacterial infections, stem cells and cell fate, and several types of cancers. These projects are representative of the types of challenges faced by many researchers on campus.

Public Health Relevance

Proteomics is the study of proteins on the broadest scale, determining the most basic information about proteins: the what, who, where and why have implications in understanding disease and disease states. Mass spectrometry is one tool which has addressed and will continue to answer these questions definitively. Applying the proven capabilities of the LTQ Orbitrap XL ETD mass spectrometer to the research described in this proposal has potential to impact human health and disease, moving research forward in numerous areas, including viral and bacterial infections, stem cells and cell fate, as well as several types of cancers.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
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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Stanford University
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Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu et al. (2017) Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension. Circulation 136:1920-1935
Mackinder, Luke C M; Chen, Chris; Leib, Ryan D et al. (2017) A Spatial Interactome Reveals the Protein Organization of the Algal CO2-Concentrating Mechanism. Cell 171:133-147.e14
Meese, Sandra; Cepeda, Andreia P; Gahlen, Felix et al. (2017) Activity-Dependent Phosphorylation by CaMKII? Alters the Ca2+ Affinity of the Multi-C2-Domain Protein Otoferlin. Front Synaptic Neurosci 9:13
Hu, Caroline K; Southey, Bruce R; Romanova, Elena V et al. (2016) Identification of prohormones and pituitary neuropeptides in the African cichlid, Astatotilapia burtoni. BMC Genomics 17:660
Ahmed, Syed Sohail; Volkmuth, Wayne; Duca, José et al. (2015) Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med 7:294ra105
Schaffer, Bethany E; Levin, Rebecca S; Hertz, Nicholas T et al. (2015) Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction. Cell Metab 22:907-21
Ziskin, Jennifer L; Greicius, Michael D; Zhu, Wan et al. (2015) Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia. Acta Neuropathol Commun 3:43
George, Paul M; Mlynash, Michael; Adams, Christopher M et al. (2015) Novel TIA biomarkers identified by mass spectrometry-based proteomics. Int J Stroke 10:1204-11
Mick, David U; Rodrigues, Rachel B; Leib, Ryan D et al. (2015) Proteomics of Primary Cilia by Proximity Labeling. Dev Cell 35:497-512
Pearson, Richard J; Morf, Laura; Singh, Upinder (2013) Regulation of H2O2 stress-responsive genes through a novel transcription factor in the protozoan pathogen Entamoeba histolytica. J Biol Chem 288:4462-74

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