The sequencing of the human genome marked the beginning of a collective scientific expedition to understand complex organisms. Genes, of course, merely contain the instructions for which proteins will populate the cell. Untangling the multi-faceted networks that regulate complex organisms and their diseases will require innovative technologies to globally monitor many classes of biomolecules, including nucleic acids, proteins, and metabolites. High-throughput technologies for gene and transcript measurement are well-developed and broadly accessible, and, as such, have had a fantastic and transformative impact on modern biology and medicine. For numerous reasons, methods for global analysis of proteins and metabolites - crucial biological effector molecules - are less evolved and markedly less accessible. The overarching mission of my program is to (1) facilitate expedient, comprehensive analysis of proteins and metabolites by innovating new mass spectrometric technologies and (2) apply these techniques to advance biomedical research. To accomplish these goals we center our efforts on four main areas: Instrumentation and Informatics, Proteomic Methodology, Metabolomics, and Biomedical Applications. First, leveraging our extensive electron transfer dissociation (ETD) development history, we plan to expand our ability to interrogate many currently intractable peptides, post-translational modification (PTMs), and other biomolecules. Second, with these and other tools, we will simplify and expedite proteome analysis; we envision analyzing an entire proteome (>10,000 proteins) or PTMome (>10,000 phosphorylation sites) in hours, or even minutes. Third, by development of novel chemical instrumentation and software tools, we will advance the field of metabolite profiling and discovery. Finally, the above mentioned technologies are most meaningfully developed in the context of relevant biology and, therefore, we plan to apply our innovative tools to many cutting-edge biomedical projects.

Public Health Relevance

The overarching mission of this project is to facilitate expedient, comprehensive analysis of proteins and metabolites by development of new chemical measurement technologies. These tools will then be applied to the study of numerous human diseases including Alzheimer's spectrum disorder, mitochondrial dysfunction, cancer, diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM118110-02S1
Application #
9416212
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Krepkiy, Dmitriy
Project Start
2016-05-05
Project End
2021-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Jha, Pooja; McDevitt, Molly T; Gupta, Rahul et al. (2018) Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species. Cell Syst 6:722-733.e6
Hebert, Alexander S; Prasad, Satendra; Belford, Michael W et al. (2018) Comprehensive Single-Shot Proteomics with FAIMS on a Hybrid Orbitrap Mass Spectrometer. Anal Chem 90:9529-9537
Mitok, Kelly A; Freiberger, Elyse C; Schueler, Kathryn L et al. (2018) Islet proteomics reveals genetic variation in dopamine production resulting in altered insulin secretion. J Biol Chem 293:5860-5877
Rhoads, Timothy W; Burhans, Maggie S; Chen, Vincent B et al. (2018) Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. Cell Metab 27:677-688.e5
Riley, Nicholas M; Westphall, Michael S; Coon, Joshua J (2018) Sequencing Larger Intact Proteins (30-70 kDa) with Activated Ion Electron Transfer Dissociation. J Am Soc Mass Spectrom 29:140-149
Lapointe, Christopher P; Stefely, Jonathan A; Jochem, Adam et al. (2018) Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis. Cell Syst 6:125-135.e6
Bucci, Michael D; Weisenhorn, Erin; Haws, Spencer et al. (2018) An Autophagy-Independent Role for ATG41 in Sulfur Metabolism During Zinc Deficiency. Genetics 208:1115-1130
Riley, Nicholas M; Coon, Joshua J (2018) The Role of Electron Transfer Dissociation in Modern Proteomics. Anal Chem 90:40-64
Wang, Yirong; Weisenhorn, Erin; MacDiarmid, Colin W et al. (2018) The cellular economy of the Saccharomyces cerevisiae zinc proteome. Metallomics 10:1755-1776
Wilson, Gary M; Blanco, Rocky; Coon, Joshua J et al. (2018) Identifying Novel Signaling Pathways: An Exercise Scientists Guide to Phosphoproteomics. Exerc Sport Sci Rev 46:76-85

Showing the most recent 10 out of 32 publications