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Elucidating Chemical Signaling Mechanisms that Regulate Multicellularity and the Transmission of Infectious Disease

Award Number: R35GM138376
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: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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Elucidating Chemical Signaling Mechanisms that Regulate Multicellularity and the Transmission of Infectious Disease - Project Summary / Abstract Organisms rarely live in isolation. They live in complex multi-species communities where soluble chemical factors mediate cell-cell signaling, cooperation, and competition. Mutualist microbes exchange metabolites and signals to benefit their hosts in myriad ways, while parasites release virulence factors that harm their hosts. Microbes also exhibit similar chemically mediated benefits and challenges to one another in environmental and host- associated contexts. From a cellular perspective, even a multicellular organism can be considered a complex symbiosis of phenotypically distinct cells using chemicals to cooperate for the overall benefit of the ‘community’. My laboratory of chemists, biochemists, and biologists aims to discover the chemical languages that shape interactions within microbial communities and between microbes and their hosts. Our proposed work focuses on chemical signaling in three distinct areas. First, we aim to uncover chemical signaling processes that regulated key transitions in the origin of the first multicellular animals (e.g., formation of multicellular bodies and differentiation of cell types). We pursue this goal by identifying the chemical signals and mechanisms that regulate multicellular behaviors in some of the closest living relatives of animals—the unicellular holozoans Capsaspora owczarzaki, Ministeria vibrans, Salpingoeca rosetta, and Corallochytrium limacisporum. This work may reveal how the first animals evolved and may inform how the diverse cells within healthy animals develop and function. Second, we aim to uncover chemical signaling processes that enable the protozoan snail symbiont Capsaspora owczarzaki to colonize its snail host. This symbiont can kill the parasitic schistosomes that mature in snails before spreading to humans where they cause the neglected tropical disease schistosomiasis. Therefore, understanding Capsaspora’s ability to persist in snails and hunt schistosomes may improve its development as a biocontrol agent to curtail the spread of schistosomes through snails near human populations. Finally, we aim to uncover new chemical signals that regulate bacterial behaviors necessary for pathogenesis. By arresting these behaviors, we can disarm pathogens. Overall, our work will reveal previously unrecognized ways that symbionts and cells within animals communicate and compete on a chemical level. This work may be applied to reveal the most fundamental mechanisms of regulated multicellularity in animals, and it also may be applied to inform efforts to curtail the transmission and virulence of infectious diseases.


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: 2025 ( Subtotal = $412,169 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	6	8/4/2025	COMPETING CONTINUATION	$412,169
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	8/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $412,169

Issue Date FY: 2024 ( Subtotal = $389,270 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	4/15/2024	NON-COMPETING CONTINUATION	$350,344
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	5	6/24/2024	NON-COMPETING CONTINUATION	$38,926
														Subtotal = $389,270

Issue Date FY: 2023 ( Subtotal = $639,205 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	4	8/2/2023	SUPPLEMENT FOR EXPANSION	$249,935
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	6/13/2023	NON-COMPETING CONTINUATION	$389,270
														Subtotal = $639,205

Issue Date FY: 2022 ( Subtotal = $389,270 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	3	4/25/2022	NON-COMPETING CONTINUATION	$389,270
														Subtotal = $389,270

Issue Date FY: 2021 ( Subtotal = $389,270 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	2	4/15/2021	NON-COMPETING CONTINUATION	$389,270
														Subtotal = $389,270

Issue Date FY: 2020 ( Subtotal = $389,270 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	1	6/26/2020	NEW	$389,270
														Subtotal = $389,270

Grand Total All Awards = $2,608,454

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Elucidating Chemical Signaling Mechanisms that Regulate Multicellularity and the Transmission of Infectious Disease

Award Number: R35GM138376

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: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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