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A general test of the genetic basis of parasite resistance across genetic and environmental contexts

Award Number: R35GM137975
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: 06/30/2025

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A general test of the genetic basis of parasite resistance across genetic and environmental contexts - Project Summary A priority in infectious disease research is to identify the genes that increase an individual’s resistance to a given infection. Variation in resistance clearly has a strong genetic basis, making it seemingly an ideal trait for identifying causal loci. Yet, genomic surveys have identified relatively few genes that consistently explain variation in disease outcomes in humans. A primary explanation for this gap is context-dependence: a gene may underlie parasite resistance at low but not high doses, or against one parasite strain but not others. This hypothesis argues that we cannot reliably detect the genes that matter for resistance without accounting for the genetic and environmental context in which hosts encounter their parasites. Ongoing projects associated with my parent award are addressing this need by characterizing genetic variation for parasite resistance across contexts using diverse host and parasite genotypes sampled from nature. Our powerful model system - the nematode Caenorhabditis elegans and its natural microsporidian parasites in the genus Nematocida – allows us to conduct highly controlled and replicated experiments across multiple contexts. We apply high-throughput phenotyping, experimental evolution, and experimental epidemiology to 1) characterize genetic variation in parasite resistance in natural populations, 2) evaluate the impact of parasite genotype on the expression of this genetic variation, and 3) examine the sensitivity of resistance genes to relevant environmental variables. Our efforts identified dose – the number of parasites a host encounters - as a major driver of the expression of genetic variation for resistance. We have designed key follow-up experiments to characterize the dose-dependency of resistance across host genotypes, and these experiments require precise estimates of parasite abundance within hosts and in their surrounding environment. Accordingly, I am requesting a supplement to this parent award to purchase a QIAcuity instrument for digital PCR to increase our precision, replication, and range of sample types for these experiments. This equipment will directly augment the impact of our projects on the scientific community and provide long-term support to my research program and department.


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 = $455,282 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	5	5/31/2024	NON-COMPETING CONTINUATION	$395,528
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	5	7/9/2024	SUPPLEMENT FOR EXPANSION	$59,754
														Subtotal = $455,282

Issue Date FY: 2023 ( Subtotal = $397,328 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	4	6/7/2023	NON-COMPETING CONTINUATION	$397,328
														Subtotal = $397,328

Issue Date FY: 2022 ( Subtotal = $397,328 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	3	6/17/2022	NON-COMPETING CONTINUATION	$397,328
														Subtotal = $397,328

Issue Date FY: 2021 ( Subtotal = $485,021 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	2	6/15/2021	NON-COMPETING CONTINUATION	$392,275
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	2	9/1/2021	SUPPLEMENT FOR EXPANSION	$92,746
														Subtotal = $485,021

Issue Date FY: 2020 ( Subtotal = $397,039 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	1	7/27/2020	NEW	$397,039
														Subtotal = $397,039

Grand Total All Awards = $2,131,998

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A general test of the genetic basis of parasite resistance across genetic and environmental contexts

Award Number: R35GM137975

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: 06/30/2025

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