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Mechanisms of asymmetric cell division during female meiosis

Award Number: R35GM136241
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Mechanisms of asymmetric cell division during female meiosis - Project Summary During female meiosis, ¾ of the chromosomes are eliminated and only ¼ of the chromosomes are inherited by a single egg. In contrast, all chromosomes are distributed among 4 sperm during male meiosis. The elimination of ¾ of the genome to allow inheritance of only ¼ of the chromosomes is conserved in all animal phyla, suggesting some fundamental selective advantage. The long-term goals of this project are to elucidate the molecular mechanisms of chromosome elimination and elucidate the selective advantages of asymmetric meiotic division. Errors in meiosis lead to the absence of one chromosome (monosomy) or the presence of an extra chromosome (trisomy) in 10-30% of human conceptions with the majority of these aneuploidies leading to embryonic death. By elucidating the mechanisms of meiotic chromosome elimination in C. elegans, we will identify mechanisms likely to be defective during human meiosis. Fertilization occurs during female meiosis in nearly all animal species. Therefore, animals must have mechanisms to prevent incorporation of paternal chromosomes into the meiotic spindle which could eliminate paternal chromosomes in a polar body causing lethal monosomy. We have demonstrated that, in C. elegans, microtubule driven transport moves the meiotic spindle to a cortical position away from the future site of fertilization. The meiotic spindle resists cytoplasmic streaming whereas the sperm contents circulate as a cohesive unit with maternal membranous organelles around the zygote. Increasing cytoplasmic streaming causes collisions between the spindle and sperm contents, however, the resulting collisions do not result in incorporation of paternal chromosomes into the meiotic spindle. We seek to elucidate the completely unexplored mechanism that holds the sperm contents together as this “goo ball” insulates paternal chromosomes from capture into the meiotic spindle. We have uncovered a second selective advantage of asymmetric meiosis by demonstrating that extra chromosomes present in trisomic or triploid C. elegans are preferentially deposited in a polar body. We seek to determine the mechanisms that preferentially move extra chromosomes toward the polar body. These mechanisms allow triploid or aneuploid C. elegans to have a high frequency of offspring with a normal chromosome number and could be relevant to the health prospects for offspring of women with triploX syndrome, trisomy 21 or mosaic trisomy. In addition, we will continue to elucidate the katanin, kinesin and dynein-dependent mechanisms ensuring bipolar meiotic spindle assembly and positioning. We will accomplish these goals by directly monitoring the movements of chromosomes and organelles by time-lapse imaging of zygotes observed in utero within transparent C. elegans after perturbations by RNA interference, auxin- induced degrons and optogenetic manipulations.


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 = $418,505 )
2026	2026	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	7	4/17/2026	NON-COMPETING CONTINUATION	$418,505
2026	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	11/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $418,505

Issue Date FY: 2025 ( Subtotal = $420,709 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	6	4/28/2025	COMPETING CONTINUATION	$420,709
2025	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	5	4/18/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	11/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $420,709

Issue Date FY: 2024 ( Subtotal = $387,741 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	2/12/2024	NON-COMPETING CONTINUATION	$348,967
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	5	7/17/2024	NON-COMPETING CONTINUATION	$38,774
														Subtotal = $387,741

Issue Date FY: 2023 ( Subtotal = $649,845 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	4	2/27/2023	SUPPLEMENT FOR EXPANSION	$27,201
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	4	2/24/2023	NON-COMPETING CONTINUATION	$387,812
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	4	7/24/2023	SUPPLEMENT FOR EXPANSION	$234,832
														Subtotal = $649,845

Issue Date FY: 2022 ( Subtotal = $462,315 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	002	3	6/23/2022	NON-COMPETING CONTINUATION	$38,802
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	3	2/16/2022	SUPPLEMENT FOR EXPANSION	$74,325
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	3	2/15/2022	NON-COMPETING CONTINUATION	$349,188
														Subtotal = $462,315

Issue Date FY: 2021 ( Subtotal = $415,255 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	2	2/24/2021	NON-COMPETING CONTINUATION	$388,054
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	2	8/18/2021	SUPPLEMENT FOR EXPANSION	$27,201
														Subtotal = $415,255

Issue Date FY: 2020 ( Subtotal = $388,107 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	1	3/25/2020	NEW	$388,107
														Subtotal = $388,107

Grand Total All Awards = $3,142,477

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Mechanisms of asymmetric cell division during female meiosis

Award Number: R35GM136241

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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