The proposed Q Exactive instrument from Thermo Scientific is a robust, high throughput, and high resolution mass spectrometer(1,2) based on high performance quadrupole mass selection and high resolution Orbitrap ion detection. It implements enhanced Fourier transform or eFT(3) algorithm for improved mass resolving power. The proposed Q Exactive instrument has several advantages over our current most powerful LTQ Orbitrap Velos instrument. The scan rate of HCD MSMS is nearly three times higher and the MSMS product ion detection efficiency is also higher. The combined effect allows the instrument to identify more peptides. As demonstrated in our comparison experiments, 2-3X more peptides are identified on the proposed instrument over those on the Velos Orbitrap. The Q Exactive mass spectrometer will help users identify and quantify post-translational modifications (PTM) from complex biological samples, determine protein complex structures, and study protein dynamics using strategically different approaches. A suite of University of California investigators will be major users and be helped in the identification and quantification of post-translational modifications (including site-specific phosphorylation and ubiquitination, fo example), proteolytically cleaved substrate networks (e.g., caspases, granzymes), host-pathogen protein interaction dynamics (HIV, T. bacillus, etc.) and drug inhibitors of kinases in patient cohorts.

Public Health Relevance

The proposed instrument will enable research projects to dissect molecular mechanisms of cellular processes, to provide a better understanding of interactions and dynamic nature of the complex molecular networks. Gaining this insight will allow systematic development of advanced medicine to treat cancers, viral infections, and neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD016229-01
Application #
8447398
Study Section
Special Emphasis Panel (ZRG1-BCMB-D (30))
Program Officer
Birken, Steven
Project Start
2013-06-15
Project End
2014-06-14
Budget Start
2013-06-15
Budget End
2014-06-14
Support Year
1
Fiscal Year
2013
Total Cost
$506,944
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bradshaw, Ralph A; Pundavela, Jay; Biarc, Jordane et al. (2015) NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling. Adv Biol Regul 58:16-27