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Mechanisms regulating spindle assembly and chromosome segregation in oocyte acentrosomal meiosis

Award Number: R35GM163783
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: 09/09/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Mechanisms regulating spindle assembly and chromosome segregation in oocyte acentrosomal meiosis - During the first meiotic division, homologous chromosomes linked by chiasmata attach to microtubules from opposite spindle poles and then separate at anaphase I. In humans, errors in chromosome separation in the oocyte leads to aneuploidy and are the leading cause of miscarriage, infertility and birth defects. Our long- term goal is to understand the mechanisms that promote accurate homologous chromosome separation during meiosis I, and the features of the oocyte spindle that make it susceptible to errors. Our previous research using Drosophila melanogaster females has led to significant insights into how chromosomes initiate spindle assembly, and how kinetochore-microtubule attachments are regulated. We have also developed several tools for the proposed studies in oocytes. These tools include RNAi resistant transgenes in order to make germline- specific mutants of key proteins. We also have the reagents, either transgenes or antibodies, to detect many of the important proteins that regulate the attachment of kinetochores to microtubules, including centromere, kinetochore, checkpoint and spindle proteins. With these tools, we will investigate the mechanisms of acentrosomal spindle assembly and the regulation of kinetochores-microtubule attachments. We will test the hypothesis that HP1 recruits the Chromosome Passenger Complex (CPC) to the chromosomes, which ensures that microtubules assemble only around the chromosomes. We will investigate the mechanisms that regulate kinetochore assembly and attachments to microtubules. These studies will focus on the kinetochore proteins SPC105R, NDC80, and the RZZ complex. We will test the hypothesis that the accurate separation of chromosomes depends on the regulating the transition between lateral attachments, where the kinetochores interact with the sides of microtubules, and end-on attachments, where the kinetochores attach to the end of microtubules. Our work has shown that the meiotic central spindle, which contains antiparallel microtubules and a high concentration of the CPC, has an important role in aligning chromosomes during prometaphase. If homologous centromeres move away from each, they can leave the CPC-rich central spindle region, which allows the kinetochores to become dephosphorylated and make end-on MT attachments to opposite spindle poles. The experiments outlined in this proposal will test these hypotheses and increase our understanding of the mechanisms of chromosome separation important to oocytes. These results and proposed studies are significant because the metaphase central spindle is a conserved structure required for separation of homologous chromosomes in acentrosomal meiosis in a variety of organisms.


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 = $431,750 )
2026	2026	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	9/9/2026	NEW	$431,750
														Subtotal = $431,750

Grand Total All Awards = $431,750

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Mechanisms regulating spindle assembly and chromosome segregation in oocyte acentrosomal meiosis

Award Number: R35GM163783

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: 09/09/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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