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Mapping and Understanding Production of Natural Products in Fungi

Award Number: R01AT009143
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Mapping and Understanding Production of Natural Products in Fungi - Project Summary/Abstract The goal of this project is to improve a genome-driven, correlation-based platform to unearth and produce new bioactive compounds from fungi. This platform and research will deliver access to a large repertoire of fungal natural products (NPs), which historically have been a great source of new medicines and useful compounds. Typical estimates have NPs and their derivatives accounting for ca. 75% of currently used antibiotics and nearly 60% of anti-cancer drugs along with numerous antiviral, antiparasitic, antifungal, and immunosuppressive medicines. Despite their historical successes, traditional screening programs have been severely curtailed due to declining numbers of promising new candidates and lack of ready access to new compounds. At the same time, analysis of over one thousand fungal genomes suggests that tens of thousands of high-value NPs have yet to be identified and screened. Thus, new technologies are needed and here we describe an integrated plan to systematically tap into this vast potential of fungal metabolites through genomics, metabolomics, bioactivity screening and molecular biology. In the previous funding period, we developed an untargeted approach called `metabologenomics' that correlates genomic content with metabolite output to uncover hundreds of new NPs and their gene clusters from soil actinobacteria. In this competing renewal, we now propose to extend the method to 300 fungi while integrating bioactivity screening in Aim 1. Activities described in this proposal will reduce technical barriers by establishing new workflows, improving experimental methodology, and refining scoring metrics to create a discovery platform with the ability to help unlock the medicinal potential of NPs in the fungal kingdom. In Aim 2, we focus on the targeted capture and expression of BGCs in specific euchromatic loci in a widely used host for NP heterologous expression, Aspergillus nidulans. The two Aims of the project describe the generation of genomic, metabolomics, bioactivity, and expression data. We further propose to make data- and milestone-driven progress on the combination of these complementary data types to systematically examine a set of 300 fungal strains. With a proven track record of deep collaboration among the team members involved, we will deliver a robust implementation of the proposed activities to provide a well-defined path to discovery of bioactive NP/BGC pairs, and study the production of new molecules from diverse fungi.


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: 2024 ( Subtotal = $517,365 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	20	5/13/2024	NON-COMPETING CONTINUATION	$517,365
														Subtotal = $517,365

Issue Date FY: 2023 ( Subtotal = $527,923 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	002	19	5/12/2023	NON-COMPETING CONTINUATION	$527,923
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	001	18	5/3/2023	COMPETING CONTINUATION	$3,450
2023	2020	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	17	5/3/2023	NON-COMPETING CONTINUATION	-$3,450
														Subtotal = $527,923

Issue Date FY: 2022 ( Subtotal = $542,923 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	002	18	8/5/2022	COMPETING CONTINUATION	$542,923
2022	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	17	3/10/2022	NON-COMPETING CONTINUATION	$0
2022	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	001	17	8/4/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $542,923

Issue Date FY: 2020 ( Subtotal = $327,308 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	17	3/13/2020	NON-COMPETING CONTINUATION	$327,308
														Subtotal = $327,308

Issue Date FY: 2019 ( Subtotal = $327,308 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	16	4/2/2019	NON-COMPETING CONTINUATION	$327,308
														Subtotal = $327,308

Issue Date FY: 2018 ( Subtotal = $327,308 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	001	15	4/24/2018	NON-COMPETING CONTINUATION	$32,731
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	15	3/23/2018	NON-COMPETING CONTINUATION	$294,577
														Subtotal = $327,308

Issue Date FY: 2017 ( Subtotal = $327,308 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	001	14	7/7/2017	NON-COMPETING CONTINUATION	$32,731
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	14	3/6/2017	NON-COMPETING CONTINUATION	$294,577
														Subtotal = $327,308

Issue Date FY: 2016 ( Subtotal = $327,308 )
2016	2016	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Research and Training in Complementary and Integrative Health	000	13	3/8/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$327,308
														Subtotal = $327,308

Grand Total All Awards = $3,224,751

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Mapping and Understanding Production of Natural Products in Fungi

Award Number: R01AT009143

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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