This project aims to enhance understanding of the aging process through the study of the long-lived Caenorhabditis elegans daf-2 mutant. A data-independent-acquisition mass spectrometry scheme will be developed to enable a high-sensitivity, high-dynamic range, quantifiable analysis of the C. elegans proteome throughout the aging process. To this end, software will be written to deconvolute MS/MS spectra derived from the fragmentation of multiple precursors. C. elegans, with a germ-line mutation to avoid development of offspring, will be synchronized and grown. Strains that will be grown include a glp-4 strain, a glp-4;daf-2 mutant strain, and a daf-16 glp-4;daf-2 mutant strain. The protein profile of these strains will be analyzed over time to uncover new components of the aging pathway as well as generate a metric for "molecular age". The relationship between "molecular age" and chronological age will be determined.

Public Health Relevance

This project will provide insight into the aging process and possibly the relationship between caloric restriction and longevity which has been observed in humans. The project will attempt to uncover the mechanism that allows a species of nematode (Caenorhabditis elegans) to double its lifespan. An understanding of this mechanism could open the door to new methods of studying and slowing human aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG037265-02
Application #
8197965
Study Section
Special Emphasis Panel (ZRG1-F04B-B (20))
Program Officer
Velazquez, Jose M
Project Start
2010-12-01
Project End
2013-10-15
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$40,672
Indirect Cost
Name
University of Washington
Department
Genetics
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Egertson, Jarrett D; Kuehn, Andreas; Merrihew, Gennifer E et al. (2013) Multiplexed MS/MS for improved data-independent acquisition. Nat Methods 10:744-6
Egertson, Jarrett D; Eng, Jimmy K; Bereman, Michael S et al. (2012) De novo correction of mass measurement error in low resolution tandem MS spectra for shotgun proteomics. J Am Soc Mass Spectrom 23:2075-82
Bereman, Michael S; Canterbury, Jesse D; Egertson, Jarrett D et al. (2012) Evaluation of front-end higher energy collision-induced dissociation on a benchtop dual-pressure linear ion trap mass spectrometer for shotgun proteomics. Anal Chem 84:1533-9