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Genomic profiling of yeast resistance to heterocyclic aromatic amine

Award Number: R15ES023685
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/09/2013
PERIOD OF PERFORMANCE END DATE: 07/31/2021

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Genomic profiling of yeast resistance to heterocyclic aromatic amine - Abstract/Summary Colorectal cancer is the second leading cause of cancer deaths in the United States. Fewer than 5% of colon cancer cases are linked to known high-penetrant genetic factors, while lifestyle factors include a diet high in red meat consumption. Carcinogens found in cooked red meat include heterocyclic aromatic amines (HAAs), which become potent DNA damaging agents after activation by P450 enzymes and N-acetyl transferase 2 (NAT2). However, it is unknown which individuals are most susceptible to HAAs and epidemiological studies often lack significance because of small sampling sizes. Since many DNA metabolism and housekeeping genes are conserved from yeast to man, high-throughput analysis of Saccharomyces cerevisiae (budding yeast) genes that confer resistance to carcinogens have identified human genes that confer resistance to environmental carcinogens. Genomic phenotyping using the ~5,000 yeast single-gene deletion haploid and diploid strains have been highly successful in determining genes that confer resistance to chemical agents. We previously were successful in introducing human CYP1A2 and CYP1A1 into yeast and activating a variety of carcinogens, including aflatoxin B1 (AFB1), benzo[a]pyrene dihydrodiol (BaP-DHD), and HAAs. The aim of this project is to determine which yeast genes are required for resistance to the potent HAA carcinogens. We will introduce plasmids that express human CYP1A2 and NAT2 into the ~5,000 diploid homozygous single-deletion strains. In the first aim, we will profile the yeast genome using the diploid single deletion strains for resistance to HAAs. Genes that confer resistance will be identified by high-throughput sensitive assays to measure cell growth and by molecular bar codes using high throughput sequencing. Considering that CYP1A2 is mostly expressed in the liver and not the colon, in the second aim, we will identify which colon-associated CYPs can metabolically activate HAAs. The information resulting from this project will aid health care providers in identifying individuals most at risk for colon cancer due to dietary carcinogens. The project will be a valuable training tool for graduate and undergraduate students in systems and cell biology.


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: 2023 ( Subtotal = -$34 )
2023	2019	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	000	3	8/23/2023	SUPPLEMENT FOR EXPANSION	-$34
														Subtotal = -$34

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	000	3	7/25/2022	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $7,982 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	000	3	5/8/2019	SUPPLEMENT FOR EXPANSION	$7,982
														Subtotal = $7,982

Issue Date FY: 2018 ( Subtotal = $445,959 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	001	3	7/26/2018	COMPETING CONTINUATION	$445,959
2018	2014	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	000	2	2/23/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $445,959

Issue Date FY: 2017 ( Subtotal = -$167 )
2017	2014	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Environmental Health	001	1	2/8/2017	NEW	-$167
2017	2014	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Environmental Health	000	1	2/8/2017	NEW	-$167
2017	2014	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Environmental Health	002	2	2/8/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$167
														Subtotal = -$167

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Environmental Health	001	2	8/9/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$141,000
2016	2014	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Environmental Health	000	1	8/9/2016	NEW	-$141,000
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $448,996 )
2014	2014	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Environmental Health	001	1	12/11/2013	NEW	$299,331
2014	2014	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Environmental Health	000	1	12/9/2013	NEW	$149,665
														Subtotal = $448,996

Grand Total All Awards = $902,736

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Genomic profiling of yeast resistance to heterocyclic aromatic amine

Award Number: R15ES023685

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/09/2013

PERIOD OF PERFORMANCE END DATE: 07/31/2021

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