The high energy collisional activation project will develop fundamental technology to improve proteomics and lipidomics. The integration of genomic and proteomic data has revealed deficiencies in the sequence coverage of proteins that are identified using conventional proteomic methods. Specifically, a minority of high value genomic variants in cancer are currently identified by state-of-the-art proteomics. This work will deploy new methods using high energy collisional activation tandem mass spectrometry on a MALDI-ToF/ToF platform that is coupled to a two dimensional high performance liquid chromatograph. The ability of HE-CAD to promote pathways of fragmentation (charge-remote fragmentation) that are not currently being used in proteomics is aimed at identifying the proteins that are expressed.
The second aim i s to apply high energy collisional activation to complex lipids, particularly those from pathogenic microorganisms. The lipids and the biosynthetic pathways that generate them in microbes are very different from mammals and thus are a potential target for therapies.

Public Health Relevance

-Public Health Relevance. The Washington University Biomedical Mass Spectrometry Resource has a longstanding history as an active and productive citizen in the NIH Biotechnology Research Resources community. We propose to extend our mission by advancing mass spectrometry technology, development, and research, applying these discoveries to answer critical biomedical research questions, and training the next generation of researchers, towards the ultimate goal of improving public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103422-41
Application #
9412484
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
41
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G et al. (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 97:1284-1298.e7
Rocha, Agostinho G; Franco, Antonietta; Krezel, Andrzej M et al. (2018) MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science 360:336-341
Frankfater, Cheryl; Jiang, Xuntian; Hsu, Fong-Fu (2018) Characterization of Long-Chain Fatty Acid as N-(4-Aminomethylphenyl) Pyridinium Derivative by MALDI LIFT-TOF/TOF Mass Spectrometry. J Am Soc Mass Spectrom 29:1688-1699
Henson, William R; Hsu, Fong-Fu; Dantas, Gautam et al. (2018) Lipid metabolism of phenol-tolerant Rhodococcus opacus strains for lignin bioconversion. Biotechnol Biofuels 11:339
Lucey, Brendan P; Hicks, Terry J; McLeland, Jennifer S et al. (2018) Effect of sleep on overnight cerebrospinal fluid amyloid ? kinetics. Ann Neurol 83:197-204
Johnson, Britney; McConnell, Patrick; Kozlov, Alex G et al. (2018) Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange. Cell Rep 23:2795-2804
Shu, Longfei; Zhang, Bojie; Queller, David C et al. (2018) Burkholderia bacteria use chemotaxis to find social amoeba Dictyostelium discoideum hosts. ISME J 12:1977-1993
Zayed, Mohamed A; Hsu, Fong-Fu; Patterson, Bruce W et al. (2018) Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques. J Lipid Res 59:730-738
Xu, Wei; Mukherjee, Sumit; Ning, Yu et al. (2018) Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana. Int J Parasitol 48:245-256
Luo, Zonghua; Rosenberg, Adam J; Liu, Hui et al. (2018) Syntheses and in vitro evaluation of new S1PR1 compounds and initial evaluation of a lead F-18 radiotracer in rodents. Eur J Med Chem 150:796-808

Showing the most recent 10 out of 323 publications