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Male x Female Protein Interactions Mediating Reproductive Success in the Drosophila Mating Plug

Award Number: F32HD111231
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Male x Female Protein Interactions Mediating Reproductive Success in the Drosophila Mating Plug - PROJECT SUMMARY In both mammals and invertebrates, initiation of post-mating responses in the female post-copulation is known to contribute to reproductive success. Seminal fluid proteins (Sfps) have been shown to initiate many of these responses. However, male x female interactions are underexplored as contributors to infertility. Investigating the mechanisms and evolution of male x female interactions is critical for understanding the complexities of reproduction. I will use D. melanogaster as a model system for investigating post-copulatory male x female interactions via characterization of male and female contributions to the Drosophila mating plug’s (MP) formation and ejection. In Drosophila, the MP forms in the uterus of the female via coagulation of male- ejaculated Sfps and some female reproductive tract proteins. Genetic disruption of the MP impacts reproductive outcomes by affecting sperm retention; however, little is known about the male and female proteins (and their interactions) that modulate mating plug ejection (MPE) rates either directly by contributing to MP composition/degradation or indirectly by regulating female ejection behavior. In Aims 1 & 2 I will respectively use female or male phenotypic variation in the Drosophila Genomic Reference Panel to perform a GWAS on MPE timing. I will then functionally investigate how top gene candidates mediate MPE timing. I have concluded a GWAS on female MPE timing and have so far identified 4 neuronal genes that regulate female MPE (Aim 1). Using highly tissue- and cell type- specific knockdown of gene candidate expression via RNA interference, I will more deeply characterize neuronal regulation of female MPE timing. After also identifying and characterizing male genes regulating MPE timing (Aim2) I will perform a 6x6 grid cross of males and females with disrupted function of MPE genes to investigate the presence of complex non-additive male x female MPE interactions. Finally, I will investigate the molecular evolution and function of male and female genes contributing to MP composition (Aim 3). I discovered that many male and female MP genes are closely paralogous to each other and evolving under positive selection, potentially suggestive of evolution under sexual conflict. After fully characterizing the evolution and coevolution of these male and female MP paralogs, I will investigate their sex-specific functions in MPE and MP formation. Observation of opposing functions for paralogous male and female MP genes would point to sexual conflict driven evolution caused by opposing sex-specific optimal mating strategies. Observation of complementary functions would indicate similar evolutionary pressures acting on male and female paralogs to cooperatively ensure optimal reproductive outcomes.


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 = $74,284 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	2	12/23/2024	NON-COMPETING CONTINUATION	$74,284
														Subtotal = $74,284

Issue Date FY: 2023 ( Subtotal = $69,080 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	1	9/21/2023	NEW	$69,080
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	1	9/21/2023	NEW	$0
														Subtotal = $69,080

Grand Total All Awards = $143,364

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Male x Female Protein Interactions Mediating Reproductive Success in the Drosophila Mating Plug

Award Number: F32HD111231

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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