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Small molecule signaling in Caenorhabditis elegans

Award Number: R01GM088290
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2010
PERIOD OF PERFORMANCE END DATE: 06/30/2019

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Small molecule signaling in Caenorhabditis elegans - DESCRIPTION (provided by applicant): The nematode Caenorhabditis elegans is one of the most important model organisms for biomedical research, because of its biological tractability and because many of its physiological pathways show strong analogies to corresponding pathways in humans. The goal of this project is to complement the highly developed genomics and proteomics of C. elegans with a comprehensive structural and functional characterization of its metabolome, which, surprisingly, has been explored to only a very limited extent. This effort is motivated by several lines of evidence indicating that small molecules of largely undetermined structure play important roles in C. elegans endocrine and exocrine signaling, specifically in key pathways regulating lifespan, development, and metabolism. Specific focus of this renewal form the biosynthesis and functions of a recently identified modular "language" of small molecules, the ascarosides, which regulate virtually every aspect of the life history of C. elegans, including lifespan. Elucidation of ascaroside biosynthesis will reveal how input from primary metabolism and conserved signaling pathways are integrated to create small-molecule signals that regulate development, aging, stress resistance, and a wide range of behaviors. Of particular interest will be the role of ascarosides in regulating C. elegans lifespan via sirtuins, a family of conserved histone deacetylases, and insulin signaling. A second focus forms the biosynthesis of bile acid-like ligands of the nuclear hormone receptor DAF-12, a homolog of vertebrate vitamin D receptors, which plays a key role in the regulation of development and lifespan downstream of ascaroside perception. Central to the proposed research is the use of synthetic derivatives of the identified signaling molecules for chemical genetic screens, as well as NMR-spectroscopic methodology that permits the analysis of complex small molecule mixtures and greatly accelerates both the structure elucidation process and the functional characterization of the detected compounds. Successful conclusion of this project will provide a partial structural and functional annotation of the C. elegans metabolome, substantially increasing our understanding of conserved pathways that control development, aging and metabolism of C. elegans and corresponding disease-relevant pathways in mammals. The small-molecule knowledge generated will not only enable future efforts aimed at more varied chemical genetic screens exploring additional aspects of the biology and ecology of C. elegans, but also of nematode species relevant in agriculture or medicine. Furthermore, methodology developed for characterizing C. elegans signaling molecules will facilitate similar studies toward structural and functional characterization of small molecule metabolites from other model organisms.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH, INC.	533 TOWER RD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	8	12/9/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $280,000 )
2017	2017	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH, INC.	533 TOWER RD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	8	6/14/2017	NON-COMPETING CONTINUATION	$280,000
														Subtotal = $280,000

Issue Date FY: 2016 ( Subtotal = $280,000 )
2016	2016	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	7	6/29/2016	NON-COMPETING CONTINUATION	$280,000
														Subtotal = $280,000

Issue Date FY: 2015 ( Subtotal = $280,000 )
2015	2015	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	6	6/30/2015	NON-COMPETING CONTINUATION	$280,000
														Subtotal = $280,000

Issue Date FY: 2014 ( Subtotal = $280,000 )
2014	2014	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	001	5	7/31/2014	COMPETING CONTINUATION	$280,000
2014	2013	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	4	7/30/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $280,000

Issue Date FY: 2013 ( Subtotal = $256,625 )
2013	2013	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	4	4/8/2013	NON-COMPETING CONTINUATION	$239,339
2013	2013	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	001	4	6/26/2013	NON-COMPETING CONTINUATION	$17,286
														Subtotal = $256,625

Issue Date FY: 2012 ( Subtotal = $265,783 )
2012	2012	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	3	4/30/2012	NON-COMPETING CONTINUATION	$265,783
														Subtotal = $265,783

Issue Date FY: 2011 ( Subtotal = $265,937 )
2011	2011	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	001	2	6/15/2011	NON-COMPETING CONTINUATION	$24,177
2011	2011	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	2	4/15/2011	NON-COMPETING CONTINUATION	$241,760
														Subtotal = $265,937

Issue Date FY: 2010 ( Subtotal = $268,481 )
2010	2010	BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH	TOWER ROAD	ITHACA	NY	14853	TOMPKINS	USA	Biomedical Research and Research Training	000	1	4/19/2010	NEW	$268,481
														Subtotal = $268,481

Grand Total All Awards = $2,176,826

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Small molecule signaling in Caenorhabditis elegans

Award Number: R01GM088290

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2010

PERIOD OF PERFORMANCE END DATE: 06/30/2019

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