The goal of this application is to develop a multidisciplinary Center for the Analysis of Cellular Mechanisms and Systems Biology, to provide new infrastructure to advance understanding of cellular mechanisms, to better understand how to overcome disease, and to build a critical mass of faculty in this area. The Center will be unique in Montana and the five surrounding states, and will include a combination of capabilities for analysis of cellular mechanisms. This project will create a powerful Mass Spectrometry and Proteomics Core infrastructure, oriented toward training researchers. Most cellular mechanisms appear to be controlled by protein post-translational modifications and the MS and Proteomics Core will add: a high resolution Qtof MS for improved "bottom up" characterization of protein post-translational modifications, an FTMS for "top-down" characterization of modifications on intact proteins, a Hyperspectral imager for enhanced multicolor proteomic multiplexing to pin-point proteins that change with biological stimulation, and a protein electro-elution system for high efficiency recovery of pin-pointed proteins. Sensitive differential protein detection capabilities developed at MSU and high sensitivity microfluidic nano LC/MS/MS will be included in the Core. New software will integrate data from an existing DNA microarray Facility. A Proteomics Reagent Synthesis Core will prepare new fluorescent reagents for differential analysis of changes in enzyme activity and post-translational modifications, that result from biological stimulation. We will build critical mass by first supporting the development of three young faculty and one senior faculty member, who is charting a new course in his research. Outstanding local and national mentors and External Advisory Committee members will guide the development of these faculty and the Center. Second, we will hire four new faculty in areas needed to build critical mass: a Chemical Biologist/Organic Synthesis expert, a Biological Mass Spectroscopist using advanced FTMS tools, a Systems Biologist working on metabolic modeling and metabolomics, and a Cell Biologist using global molecular tools. Outstanding MSU Institutional Support ($1,400,000), the significance and timeliness of the post-genomic analysis of cellular mechanisms, and the orientation toward training in advanced methods will seed new projects-and will result in significant scientific contributions and a sustainable Center.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
3P20GM103394-05S1
Application #
8605372
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Caldwell, Sheila
Project Start
2008-09-26
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$1,129,751
Indirect Cost
$342,146
Name
Montana State University - Bozeman
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
Zignego, Donald L; Hilmer, Jonathan K; June, Ronald K (2015) Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids. J Biomech 48:4253-61
Ammons, Mary Cloud B; Morrissey, Kathryn; Tripet, Brian P et al. (2015) Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds. PLoS One 10:e0126735
Jutila, Aaron A; Zignego, Donald L; Schell, William J et al. (2015) Encapsulation of chondrocytes in high-stiffness agarose microenvironments for in vitro modeling of osteoarthritis mechanotransduction. Ann Biomed Eng 43:1132-44
Hamerly, Timothy; Tripet, Brian P; Tigges, Michelle et al. (2015) Untargeted metabolomics studies employing NMR and LC-MS reveal metabolic coupling between Nanoarcheum equitans and its archaeal host Ignicoccus hospitalis. Metabolomics 11:895-907
Jutila, Aaron A; Zignego, Donald L; Hwang, Bradley K et al. (2014) Candidate mediators of chondrocyte mechanotransduction via targeted and untargeted metabolomic measurements. Arch Biochem Biophys 545:116-23
Ammons, Mary Cloud B; Tripet, Brian P; Carlson, Ross P et al. (2014) Quantitative NMR metabolite profiling of methicillin-resistant and methicillin-susceptible Staphylococcus aureus discriminates between biofilm and planktonic phenotypes. J Proteome Res 13:2973-85
Heinemann, Joshua; Noon, Brigit; Mohigmi, Mohammad J et al. (2014) Real-time digitization of metabolomics patterns from a living system using mass spectrometry. J Am Soc Mass Spectrom 25:1755-62
Fonner, Brittany A; Tripet, Brian P; Lui, Mengyao et al. (2014) ¹H, ¹³C, ¹⁵N backbone and side chain NMR resonance assignments of the N-terminal NEAr iron transporter domain 1 (NEAT 1) of the hemoglobin receptor IsdB of Staphylococcus aureus. Biomol NMR Assign 8:201-5
Sonsteng, Katherine M; Prigge, Justin R; Talago, Emily A et al. (2014) Hydrodynamic delivery of Cre protein to lineage-mark or time-stamp mouse hepatocytes in situ. PLoS One 9:e91219
Zignego, Donald L; Jutila, Aaron A; Gelbke, Martin K et al. (2014) The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes. J Biomech 47:2143-8

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