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Timing and regulation of meiotic commitment

Award Number: R01GM105755
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: 08/01/2014
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Timing and regulation of meiotic commitment - Project Summary/Abstract: Meiosis is the cell division process in which a diploid cell undergoes one round of DNA replication followed by two rounds of chromosome segregation to ultimately produce haploid gametes. Errors in meiotic chromosome segregation can result in miscarriage and trisomy conditions, such as Down syndrome. Therefore, studying meiotic chromosome segregation is important for understanding how errors in this process occur. The objective of this proposal is to determine the mechanisms that regulate proper chromosome segregation, focusing on unique events in meiosis I and meiosis II. These studies leverage the model organism S. cerevisiae, due to the ease of developing tools to address mechanistic questions. These innovative tools will allow the investigation of how cells establish microtubule-kinetochore attachments, how cells correct improper attachments, and how cells monitor the attachments through spindle checkpoint activity, which delays the cell cycle in the presence of unattached kinetochores. The rationale for the proposed research is that the questions focus on processes that are unique to meiosis but are likely to be highly conserved, allowing the findings in budding yeast to uncover general mechanisms of meiotic regulation. Strong preliminary data guide the following three specific aims: 1) determine how the number of crossovers and crossover position along the chromosome affects the establishment of correct kinetochore-microtubule attachments in meiosis I; 2) investigate how cells prevent persistent spindle checkpoint activity during meiosis; and, 3) determine how the phophoregulation of proteins at the meiotic kinetochore ensure proper kinetochore-microtubule attachments in meiosis II. In the first aim, strains have been developed to target crossovers at particular locations on a chromosome arm. Using time-lapse imaging, the strains will be monitored for the timing of establishing bioriented kinetochore microtubule attachments, and for the number of rounds of error correction of improper attachments. The second aim tests the novel hypothesis that cells have a developmentally programmed mechanism to overcome persistent spindle checkpoint activity in meiosis to ensure the production of gametes. The third aim analyzes how protein phosphatases counteract kinase activity to specifically ensure kinetochore assembly and the establishment of kinetochore-microtubule attachments specifically in meiosis II. The innovative approach of combining the latest imaging technologies to monitor kinetochore-microtubule attachments in engineered strains allows the testing of novel hypotheses about cell-cycle regulation. The proposed research is significant because the results are expected to reveal general principles of meiotic regulation important for proper chromosome segregation. Ultimately, the results will further our understanding of how errors in meiosis facilitate developmental abnormalities.


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 = $305,533 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	11	3/25/2025	NON-COMPETING CONTINUATION	$305,533
														Subtotal = $305,533

Issue Date FY: 2024 ( Subtotal = $541,623 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	10	3/19/2024	COMPETING CONTINUATION	$356,626
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	005	10	7/23/2024	COMPETING CONTINUATION	$29,032
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	006	10	8/29/2024	SUPPLEMENT FOR EXPANSION	$184,997
2024	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	004	9	7/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$29,032
2024	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	003	9	7/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$28,888
2024	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	9	3/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	002	8	7/16/2024	NON-COMPETING CONTINUATION	-$28,888
														Subtotal = $541,623

Issue Date FY: 2023 ( Subtotal = $326,500 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	9	6/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$326,500
2023	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	8	6/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $326,500

Issue Date FY: 2022 ( Subtotal = $304,979 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	8	12/8/2021	NON-COMPETING CONTINUATION	$274,481
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	8	8/1/2022	NON-COMPETING CONTINUATION	$30,498
														Subtotal = $304,979

Issue Date FY: 2021 ( Subtotal = $321,157 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	7	12/10/2020	NON-COMPETING CONTINUATION	$274,768
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	002	7	9/13/2021	SUPPLEMENT FOR EXPANSION	$15,860
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	7	2/23/2021	NON-COMPETING CONTINUATION	$30,529
														Subtotal = $321,157

Issue Date FY: 2020 ( Subtotal = $326,232 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	004	6	9/5/2020	COMPETING CONTINUATION	$49,186
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	002	6	2/26/2020	COMPETING CONTINUATION	$326,232
2020	2018	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	003	5	9/5/2020	SUPPLEMENT FOR EXPANSION	-$49,186
2020	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	5	2/25/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	2/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $326,232

Issue Date FY: 2018 ( Subtotal = $376,887 )
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	6/22/2018	NON-COMPETING CONTINUATION	$295,318
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	001	5	9/14/2018	SUPPLEMENT FOR EXPANSION	$81,569
														Subtotal = $376,887

Issue Date FY: 2017 ( Subtotal = $295,556 )
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	205C BRYAN HALL, 105 N INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	6/8/2017	NON-COMPETING CONTINUATION	$295,556
														Subtotal = $295,556

Issue Date FY: 2016 ( Subtotal = $295,781 )
2016	2016	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	3	6/24/2016	NON-COMPETING CONTINUATION	$295,781
														Subtotal = $295,781

Issue Date FY: 2015 ( Subtotal = $295,996 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	2	6/30/2015	NON-COMPETING CONTINUATION	$295,996
														Subtotal = $295,996

Issue Date FY: 2014 ( Subtotal = $296,201 )
2014	2014	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	1	7/25/2014	NEW	$296,201
														Subtotal = $296,201

Grand Total All Awards = $3,686,445

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Timing and regulation of meiotic commitment

Award Number: R01GM105755

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: 08/01/2014

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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