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Defining the contributions of apoptosis to germline syncytium function during oogenesis

Award Number: F32HD117621
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: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Defining the contributions of apoptosis to germline syncytium function during oogenesis - Project Summary/Abstract The health of female gametes (oocytes) decreases exponentially as maternal age increases causing infertility and miscarriage risks. Infertility affects at least 1 in 4 women of childbearing age in North America and more worldwide. While medical interventions including in vitro fertilization (IVF) have improved reproductive success, this is strongly dependent on gamete health. In a human female, oocyte production (oogenesis) begins before birth where two-thirds of precursor oocytes are normally eliminated by programmed cell death (apoptosis). The few germline cells that escape apoptosis mature into oocytes. Apoptosis affects oocyte quality through unknown mechanisms. Studies on the contribution of apoptosis to maternal fertility are limited due to challenges with performing experiments on humans and even mice, and an underrepresentation of women's health studies in science. Identifying mechanisms that promote oocyte health will enhance our understanding of factors leading to infertility and aid fertility health research. Organ structure is tightly coupled to function, and the ovaries where oocytes are made are no exception. Throughout animal phylogeny, oogenic germlines are syncytial; they comprise of large, elaborate cells wherein many nuclei reside in connected compartments. My preliminary work with the oogenic germline of the model animal Caenorhabditis elegans revealed that disrupting germline structure prevented apoptosis and decreased fertility. How apoptosis removes certain precursor oocytes at the expense of others is unknown. The goal of this study is to determine the role of apoptosis in oogenesis and oocyte health as a conserved mechanism like apoptosis may explain ovary autonomous mechanisms in place to control oocyte quality before ovulation. The experiments proposed will be performed using the oogenic germline of C. elegans, due to similarities in proportional time scales of age-related oocyte quality decline and syncytial nature of precursor oocytes within the ovary. C. elegans has profound experimental advantages including a simple regulation of apoptosis. The proposed work will be conducted under the mentorship of Dr. Amy Shaub Maddox, with valued collaborators and a vibrant scientific community. Dr. Maddox has extensive experience with C. elegans, contractility, cell shape regulation, advanced imaging methods, and theoretical modeling. The lab is well-equipped with all the tools necessary to define the interplay between apoptosis in germline architecture and function. This project provides a comprehensive training opportunity for me by teaching me animal physiology and cell biology, microscopy and data analysis, and mathematical modeling. I will obtain professional development through mentoring undergraduates, attending networking events, writing, and publishing my work, and presenting at cell biology conferences like the Triangle Cytoskeleton and the American Society for Cell Biology meetings, with the ultimate goal of becoming an independent scientist faculty member at a research university in the US.


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 = $80,236 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	2	4/2/2026	NON-COMPETING CONTINUATION	$79,348
2026	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	1	2/13/2026	NEW	$888
														Subtotal = $80,236

Issue Date FY: 2025 ( Subtotal = $74,632 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	003	1	1/14/2025	NEW	$0
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	002	1	1/14/2025	NEW	$0
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	1	1/14/2025	NEW	$0
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	004	1	6/2/2025	NEW	$1,224
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	1	1/6/2025	NEW	$73,408
														Subtotal = $74,632

Grand Total All Awards = $154,868

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Defining the contributions of apoptosis to germline syncytium function during oogenesis

Award Number: F32HD117621

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: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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