Nuclear-cytoplasmic interactions in mammalian embryos

哺乳动物胚胎中的核-细胞质相互作用

基本信息

  • 批准号:
    RGPIN-2015-06228
  • 负责人:
  • 金额:
    $ 2.04万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

Reproductive success is the single most important measurement of progress of animal breeding programs. However, reproductive success in high-performing domestic animals is significantly compromised by elevated embryonic mortality during gestation and postnatal morbidity. This is particularly true in gestations resulting from assisted reproductive techniques (ART) such as the in vitro production of embryos and somatic cell nuclear transfer (SCNT). In these animals, little is known of the etiology of the developmental abnormalities associated with ART, which include the Large Offspring Syndrome, indicating that further research is needed to elucidate the biological mechanisms and to improve the efficiency of ART for animal breeding practices. Therefore, my research interests are aimed at exploring the epigenetic phenomena of cell reprogramming with emphasis on those involved in the pre- and postnatal developmental losses caused by ART. Chromatin remodeling is a key feature of the successful reprogramming by SCNT and in derivation of induced pluripotent stem (iPS) cells. Genomic imprinting is an epigenetic phenomenon that enables the monoallelic expression of a group of developmentally important genes in a parent-of-origin fashion through the allele-specific methylation of differentially methylated regions. Since most imprinted genes have been studied in laboratory animals, preliminary characterization of these imprinted control regions is required to enable studies in the large animals. Therefore, my principal objective is to improve our understanding of the epigenetic interactions between nuclei and cytoplasm during chromatin remodelling in mammals, particularly in domestic species. Our hypothesis is that the reprogramming of somatic cell nuclei involves epigenetic modification directed by cytoplasmic components that allow normal spatial and temporal patterns of gene expression during early development. The specific objectives are to (1) characterize the epigenetic anomalies associated with success and failure during development of embryos derived by ART, particularly in vitro fertilization and consequent in vitro culture, SCNT and pluripotent stem cells, and (2) investigate the molecular mechanisms controlling the erasure and establishment of epigenetic marks in the differentially methylated regions of imprinted genes and their parental-specific and overall expression patterns. Together, the findings from this research program will have significant impact on our understanding of the epigenetic mechanisms of chromatin reprogramming during early development in large domestic animals, providing a better understanding of how the oocyte is able to effectively reprogram somatic nuclei. In practice, these studies will enable the creation of novel and improved tools that assure a safe and efficient use of ART in farm animal breeding practices.**
繁殖成功率是衡量动物育种计划进展的最重要指标。然而,高性能家畜的繁殖成功率受到妊娠期胚胎死亡率和产后发病率升高的严重影响。 这在辅助生殖技术(ART)如体外生产胚胎和体细胞核移植(SCNT)引起的妊娠中尤其如此。在这些动物中,与ART相关的发育异常的病因学知之甚少,包括大型后代综合征,这表明需要进一步研究以阐明生物学机制并提高ART用于动物育种实践的效率。我的研究兴趣旨在探索细胞重编程的表观遗传现象,重点是那些参与前,染色质重塑是SCNT成功重编程和诱导多能干细胞(iPS)衍生的关键特征。基因组印记是一种表观遗传现象,其通过差异甲基化区域的等位基因特异性甲基化,使一组发育重要基因以起源亲本的方式单等位基因表达。由于大多数印迹基因已在实验室动物中进行了研究,因此需要对这些印迹控制区域进行初步表征,以便在大型动物中进行研究。因此,我的主要目标是提高我们对哺乳动物,特别是家养动物的染色质重塑过程中细胞核和细胞质之间的表观遗传相互作用的理解。我们的假设是,体细胞核的重编程涉及由细胞质成分指导的表观遗传修饰,这些细胞质成分允许在早期发育期间基因表达的正常空间和时间模式。具体目标是(1)表征与ART衍生胚胎发育过程中成功和失败相关的表观遗传异常,特别是体外受精和随后的体外培养、SCNT和多能干细胞,探讨印迹基因及其亲本差异甲基化区域表观遗传标记的擦除和建立的分子机制。具体和总体表达模式。总之,这项研究计划的发现将对我们理解大型家畜早期发育过程中染色质重编程的表观遗传机制产生重大影响,从而更好地了解卵母细胞如何能够有效地重编程体细胞核。在实践中,这些研究将有助于创造新的和改进的工具,确保在农场动物育种实践中安全有效地使用ART。

项目成果

期刊论文数量(0)
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Smith, Lawrence其他文献

Demands, resources, and work ability: A cross-national examination of health care workers
Cultivating Empathy Through Virtual Reality: Advancing Conversations About Racism, Inequity, and Climate in Medicine
  • DOI:
    10.1097/acm.0000000000003615
  • 发表时间:
    2020-12-01
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Roswell, Robert O.;Cogburn, Courtney D.;Smith, Lawrence
  • 通讯作者:
    Smith, Lawrence
Supportive programs increase medical students' research interest and productivity
  • DOI:
    10.2310/6650.2006.05013
  • 发表时间:
    2006-05-01
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Zier, Karen;Friedman, Erica;Smith, Lawrence
  • 通讯作者:
    Smith, Lawrence
Voxel Printing Anatomy: Design and Fabrication of Realistic, Presurgical Planning Models through Bitmap Printing
  • DOI:
    10.3791/63214
  • 发表时间:
    2022-02-01
  • 期刊:
  • 影响因子:
    1.2
  • 作者:
    Jacobson, Nicholas M.;Smith, Lawrence;MacCurdy, Robert
  • 通讯作者:
    MacCurdy, Robert
SHIFT SCHEDULE, WORK-FAMILY RELATIONSHIPS, MARITAL COMMUNICATION, JOB SATISFACTION AND HEALTH AMONG TRANSPORT SERVICE SHIFT WORKERS

Smith, Lawrence的其他文献

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{{ truncateString('Smith, Lawrence', 18)}}的其他基金

Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2020-05278
  • 财政年份:
    2022
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Biparental haploid cells to generate genomically designed offspring
双亲单倍体细胞产生基因组设计的后代
  • 批准号:
    536636-2018
  • 财政年份:
    2021
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Research and Development Grants
Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2020-05278
  • 财政年份:
    2021
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Biparental haploid cells to generate genomically designed offspring
双亲单倍体细胞产生基因组设计的后代
  • 批准号:
    536636-2018
  • 财政年份:
    2020
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Research and Development Grants
Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2020-05278
  • 财政年份:
    2020
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Biparental haploid cells to generate genomically designed offspring
双亲单倍体细胞产生基因组设计的后代
  • 批准号:
    536636-2018
  • 财政年份:
    2019
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Research and Development Grants
Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2015-06228
  • 财政年份:
    2018
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Use of haploid embryonic cells to generate offspring with predetermined genomes
使用单倍体胚胎细胞产生具有预定基因组的后代
  • 批准号:
    487107-2015
  • 财政年份:
    2017
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Research and Development Grants
Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2015-06228
  • 财政年份:
    2017
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Nuclear-cytoplasmic interactions in mammalian embryos
哺乳动物胚胎中的核-细胞质相互作用
  • 批准号:
    RGPIN-2015-06228
  • 财政年份:
    2016
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual

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