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REGULATION OF GAMETE USE AND NEURAL PATHWAYS IN REPRODUCTION

Award Number: R01HD059060
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/24/2009
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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REGULATION OF GAMETE USE AND NEURAL PATHWAYS IN REPRODUCTION - PROJECT SUMMARY Sexual reproduction requires precise orchestration of expression of myriad genes in males and females. These genes mediate interactions between the sexes at molecular, cellular, neural and whole- organism levels, including the differential fertility success of sperm from two competing males that mate to a single female. In the current funding period, we used the tractable Drosophila model system to dissect the role of genes expressed in octopaminergic neurons in differential sperm use by a multiply-mated female. In this renewal application, we propose as Aim 1 a set of experiments that identify genes and quantify their effects on mating plug ejection, a proximal phenotype with a key role in sperm competition outcomes. Mating plug ejection timing allows females to exert control over paternity of their future offspring. Early ejection of a mating plug disadvantages the male by decreasing the number of his sperm that can be used; conversely longer retention of the plug gives the male a paternity advantage. Both males and females contribute to the mating plug and its ejection. After completing a GWAS for female and male determinants of mating plug ejection timing and validating the resulting genes, we will perform a grid cross to determine whether variation in mating plug timing is mostly determined by genetic variation in the male, or the female, or an interaction between the two. Follow-up perturbation of those genes will begin to unravel genetic pathways linking male quality or its perception with mating plug ejection. In Aim 2, we will pursue the implications of our recent discovery that mating induces differential exon or promoter use by a large suite of genes in the female brain. Intriguingly, two of these genes, desat1 and foraging, act in mating discrimination or other reproductive- relevant behaviors. Each strongly activates one of four alternative promoters in response to mating. We will survey the transcriptome to quantify how variation in male factors drive post-mating differential transcript use, how the latter varies across female genotypes, and how this regulation occurs. In Aim 3 we extend and generalize models designed to quantify and predict outcomes of pairwise interactions. The classical Bradley-Terry model, widely applied in predicting outcomes of sporting contests between teams that have not yet competed, has a direct analogy in sperm competition “contests.” Assessing fit to models of this class will test whether the males’ fitness can be rank-ordered, and whether those rank orders produce accurate outcome predictions. We will extend these models to the outcomes of the experiments in Aims 1 and 2, and those performed in this project over the years, using the results to assess the overall importance of male x female interactions in each case. Many of the processes that we will study show high levels of evolutionary conservation, implying that our results will expand our understanding of male x female interactions in reproduction that may have relevance to cases of idiopathic human infertility that may involve genetic incompatibility between the partners.


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 = $335,916 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	16	7/11/2025	NON-COMPETING CONTINUATION	$335,916
2025	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	15	11/15/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $335,916

Issue Date FY: 2024 ( Subtotal = $421,637 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	15	5/4/2024	NON-COMPETING CONTINUATION	$332,864
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	15	5/6/2024	SUPPLEMENT FOR EXPANSION	$88,773
														Subtotal = $421,637

Issue Date FY: 2023 ( Subtotal = $426,171 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	002	14	4/17/2023	NON-COMPETING CONTINUATION	$336,502
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	003	14	5/24/2023	SUPPLEMENT FOR EXPANSION	$89,669
2023	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	13	3/21/2023	COMPETING CONTINUATION	$53,603
2023	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	12	3/21/2023	NON-COMPETING CONTINUATION	-$53,603
														Subtotal = $426,171

Issue Date FY: 2022 ( Subtotal = $336,750 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	13	3/25/2022	COMPETING CONTINUATION	$336,750
														Subtotal = $336,750

Issue Date FY: 2021 ( Subtotal = $301,201 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	12	4/13/2021	NON-COMPETING CONTINUATION	$301,201
														Subtotal = $301,201

Issue Date FY: 2020 ( Subtotal = $307,848 )
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	11	4/15/2020	NON-COMPETING CONTINUATION	$307,848
														Subtotal = $307,848

Issue Date FY: 2019 ( Subtotal = $308,292 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	10	4/2/2019	NON-COMPETING CONTINUATION	$308,292
														Subtotal = $308,292

Issue Date FY: 2018 ( Subtotal = $332,345 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	003	9	8/21/2018	SUPPLEMENT FOR EXPANSION	$23,658
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	002	9	6/27/2018	NON-COMPETING CONTINUATION	$308,687
2018	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	8	12/6/2017	COMPETING CONTINUATION	$7,796
2018	2016	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	7	12/6/2017	EXTENSION WITH OR WITHOUT FUNDS	-$7,796
														Subtotal = $332,345

Issue Date FY: 2017 ( Subtotal = $309,039 )
2017	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	8	3/8/2017	COMPETING CONTINUATION	$309,039
														Subtotal = $309,039

Issue Date FY: 2016 ( Subtotal = $310,471 )
2016	2016	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	7	7/8/2016	EXTENSION WITH OR WITHOUT FUNDS	$310,471
														Subtotal = $310,471

Issue Date FY: 2015 ( Subtotal = $334,366 )
2015	2015	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	6	7/9/2015	NON-COMPETING CONTINUATION	$334,366
														Subtotal = $334,366

Issue Date FY: 2014 ( Subtotal = $403,595 )
2014	2014	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	001	5	8/6/2014	NON-COMPETING CONTINUATION	$368,103
2014	2014	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	4	1/15/2014	SUPPLEMENT FOR EXPANSION	$35,492
														Subtotal = $403,595

Issue Date FY: 2013 ( Subtotal = $297,915 )
2013	2013	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	4	7/12/2013	NON-COMPETING CONTINUATION	$297,915
														Subtotal = $297,915

Issue Date FY: 2012 ( Subtotal = $314,016 )
2012	2012	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Child Health and Human Development Extramural Research	000	3	4/16/2012	COMPETING CONTINUATION	$314,016
														Subtotal = $314,016

Issue Date FY: 2010 ( Subtotal = $380,652 )
2010	2010	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Trans-NIH Recovery Act Research Support	000	2	8/4/2010	NON-COMPETING CONTINUATION	$380,652
														Subtotal = $380,652

Issue Date FY: 2009 ( Subtotal = $381,302 )
2009	2009	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Trans-NIH Recovery Act Research Support	000	1	8/21/2009	NEW	$381,302
														Subtotal = $381,302

Grand Total All Awards = $5,501,516

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REGULATION OF GAMETE USE AND NEURAL PATHWAYS IN REPRODUCTION

Award Number: R01HD059060

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/24/2009

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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