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The causes of balancing selection on immunity genes: from populations to molecular interactions.

Award Number: R01AI139154
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Immunity is an enormously important topic for human health with economic costs of infectious disease eclipsing $100 billion in 2014. At the same time, the evolution of the immune system is fertile ground for the study of evolutionary processes because a) natural selection on immunity is intense since the outcome of infection is often life or death and b) pathogens have the ability to respond to host adaptation leading to rapid evolution through an evolutionary arms race. Since insects lack an adaptive immune system, they are excellent models to understand the molecular genetics and evolution of innate immunity. An important component of innate immunity is the complement of antimicrobial peptides (AMPs) that are produced and secreted by host cells upon infection and directly inhibit pathogens. Variation in the genes encoding these AMPs is often maintained by balancing selection, the process by which multiple alleles are maintained at the same locus through various mechanisms. While instances of balancing selection are being reported more and more frequently, we lack a comprehensive understanding of the mechanistic basis of balancing selection in most examples. The ability to connect broad scale patterns of DNA sequence diversity to mechanistic differences in protein function is innovative and would provide a comprehensive view of balancing selection. Furthermore, the identification of particular amino acid polymorphisms that are maintained by balancing selection facilitates the mechanistic study of balancing selection because the presumptive causative mutations are known a priori. Our use of Drosophila as a model system also allows for study of AMP variation in vivo in a way that is much more cost effective than several other model systems, while allowing the flexibility to move between in vitro and whole organism in vivo study. These peptides are ideal for the functional study of balancing selection because a) genetic variation in several peptides is maintained by balancing selection, providing replication, b) AMPs are effectors and thus interact directly with pathogens and c) AMPs are small and can be easily studied in vitro. Aim 1 involves determining peptide differences in vitro to understand how single amino acid changes lead to different function. Aim 2 will determine the effect of AMP variation on the entire organism and investigate the role of life history tradeoffs in balancing selection. The project is significant because it will provide a deeper understanding of evolutionary processes by uncovering molecular mechanisms and may provide a better understanding of innate immunity to enhance our treatment of human disease.


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 = -$11,477 )
2025	2022	UNIVERSITY OF KANSAS CENTER FOR RESEARCH INC	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	5	11/22/2024	NON-COMPETING CONTINUATION	-$11,477
														Subtotal = -$11,477

Issue Date FY: 2022 ( Subtotal = $363,915 )
2022	2022	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	5	4/13/2022	NON-COMPETING CONTINUATION	$363,915
														Subtotal = $363,915

Issue Date FY: 2021 ( Subtotal = $363,937 )
2021	2021	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	4	4/16/2021	NON-COMPETING CONTINUATION	$363,937
														Subtotal = $363,937

Issue Date FY: 2020 ( Subtotal = $365,300 )
2020	2020	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	3	4/10/2020	NON-COMPETING CONTINUATION	$365,300
														Subtotal = $365,300

Issue Date FY: 2019 ( Subtotal = $369,800 )
2019	2019	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	2	4/19/2019	NON-COMPETING CONTINUATION	$369,800
														Subtotal = $369,800

Issue Date FY: 2018 ( Subtotal = $391,218 )
2018	2018	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	1	5/17/2018	NEW	$391,218
														Subtotal = $391,218

Grand Total All Awards = $1,842,693

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The causes of balancing selection on immunity genes: from populations to molecular interactions.

Award Number: R01AI139154

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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