Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis

女性减数分裂过程中控制染色体分离的信号机制

基本信息

  • 批准号:
    10457384
  • 负责人:
  • 金额:
    $ 38.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-17 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary Meiosis is the cell division process that is essential for sexual reproduction because it creates haploid gametes from diploid precursor cells. Chromosome segregation during meiosis I (MI) is unique because replicated sister chromatids remain attached to one another while homologous chromosome pairs segregate. In humans, mistakes in MI occur are strikingly high in female gametes (oocytes), resulting in infertility, miscarriage, or birth defects, yet the molecular mechanisms that control MI are poorly understood. Work in our lab has been instrumental in dissecting the signaling mechanisms used to control MI to explain this phenomenon. The Aurora protein kinase family is comprised of three members: AURKA, AURKB and AURKC. The AURKs are essential regulators of chromosome segregation in mitosis, and their activities are required for completing MI chromosome segregation. AURKC expression is limited to gametes and is aberrantly expressed in some cancers. Yet, because AURKC shares high sequence homology with AURKB standard approaches to understand their MI-specific functions were not sufficient. Our expertise in creating and evaluating oocyte- specific AURK knockout mice has afforded us the ability to unravel the mystery of why oocytes contain two kinases that are similar to one another. Not only have we identified AURKB and AURKC functions that are distinct from one another, we have discovered that the three AURKs regulate one another. In this proposal, we aim to continue to dissect the requirements for each AURK during MI, and to determine how and why the AURKs regulate one another. By studying the functions of all three AURK family members, we will uncover the evolutionary benefit and the consequences of expressing three AURKs. To do so we will: 1) Elucidate how AURKA and AURKC counter-acting activities are required to build an MI spindle, 2) examine cell lines that aberrantly express AURKC to determine if these counter-acting activities drive aneuploidy in mitosis, and 3) determine how AURKB regulates proteins required for the spindle assembly checkpoint during MI. Information gained from our studies will help us fully understand how these kinases operate during MI while highlighting distinct differences between how mitosis and MI are controlled. Importantly, these data will shed light on how MI chromosome segregation is controlled in oocytes and why it commonly goes awry in women leading to aneuploidy.
项目总结

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Karen A Schindler其他文献

Karen A Schindler的其他文献

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{{ truncateString('Karen A Schindler', 18)}}的其他基金

Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10683357
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10332058
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10455188
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis (Equipment Administrative Supplement)
女性减数分裂过程中控制染色体分离的信号机制(设备管理补充)
  • 批准号:
    10405164
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10581965
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10682324
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis
女性减数分裂过程中控制染色体分离的信号机制
  • 批准号:
    10265406
  • 财政年份:
    2020
  • 资助金额:
    $ 38.75万
  • 项目类别:
Association of the Maternal Exome with Risk of an Aneuploid Conception
母体外显子组与非整倍体受孕风险的关联
  • 批准号:
    10307609
  • 财政年份:
    2017
  • 资助金额:
    $ 38.75万
  • 项目类别:
Understanding genetic risk for aneuploid conception
了解非整倍体受孕的遗传风险
  • 批准号:
    10585662
  • 财政年份:
    2017
  • 资助金额:
    $ 38.75万
  • 项目类别:
Association of the Maternal Exome with Risk of an Aneuploid Conception
母体外显子组与非整倍体受孕风险的关联
  • 批准号:
    10063883
  • 财政年份:
    2017
  • 资助金额:
    $ 38.75万
  • 项目类别:

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A model for statistics of the biological cell division process
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  • 批准号:
    521924-2018
  • 财政年份:
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  • 资助金额:
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  • 项目类别:
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