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Systematic Genetic Identification of Resistance Determinants and Fitness Modifiers in Malaria Parasites

Award Number: F31AI197667
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/13/2026
PERIOD OF PERFORMANCE END DATE: 08/12/2028

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Systematic Genetic Identification of Resistance Determinants and Fitness Modifiers in Malaria Parasites - PROJECT SUMMARY Globally, approximately 282 million incidences and 610,000 fatalities were attributed to malaria in 2024 (World Malaria Report, 2025). The recent increase in cases highlights the urgent need for a more comprehensive understanding of the etiological agent of the disease. The protozoan parasite responsible for causing malaria, Plasmodium falciparum, remains the most prevalent and lethal species among the Plasmodium genera. Malaria persistence can be partly attributed to the growing resistance of the Plasmodium parasite to currently available antimalarial drugs (World Malaria Report, 2025). An additional factor to the difficulty of eradication efforts is the highly competitive nature of Plasmodium falciparum populations in Africa, where the emergence and spread of drug resistance pose significant challenges to malaria control1–4. I propose conducting bulk segregant analyses (BSAs), both with and without artemisinin (ART) pressure, with sample collection at multiple time points. Previous BSAs under drug pressure have successfully uncovered key mutations such as pfCRT for chloroquine (CQ) resistance and pfK13 for ART resistance5,6. However, these methodologies required careful refinement and are still being optimized for other drugs, such as piperaquine (PPQ). Based on my preliminary data and prior in vivo pooled assays, I hypothesize that competitive dynamics and resistance mechanisms interact in ways that complicate resistance detection and parasite population structure under temporary selective pressure7–9. Combining genetically diverse parasites in pooled assays can confound the detection of resistance when drug sensitivity varies among the population. In such cases, the resistant parasite can only be detected through genetic sequencing and tracking the most abundant parasite. Furthermore, competition among parasites plays a significant role in population dynamics. More fit parasites, even if drug-sensitive, may outcompete resistant parasites and dominate the population after treatment. Interestingly, moderately resistant and moderately fit parasites may emerge as dominant when no parasites exhibit both high fitness and high resistance. Utilizing the experimental structure of a competitive growth assay in a genetic cross will assess fitness-resistance trade-offs by monitoring allelic shifts under both treated and untreated conditions. These experiments will provide insights into how genetic architecture influences competitive outcomes and facilitates the spread of resistant parasites. This work aligns with global malaria control efforts by providing critical data on the evolutionary dynamics of resistance, informing surveillance strategies, and guiding intervention policies.


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: 2026 ( Subtotal = $50,114 )
2026	2026	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	001	1	8/5/2026	NEW	$0
2026	2026	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	1	8/5/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Systematic Genetic Identification of Resistance Determinants and Fitness Modifiers in Malaria Parasites

Award Number: F31AI197667

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/13/2026

PERIOD OF PERFORMANCE END DATE: 08/12/2028

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