Structural and Functional Studies of Nuclear Organization, Chromatin and Chromosome Behaviour during Nuclear Division

核分裂过程中核组织、染色质和染色体行为的结构和功能研究

• 批准号: RGPGP-2015-00071
• 负责人: Riggs, Charles
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Group
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612462
• 关键词: Structural; Functional; Studies; Nuclear; Organization

We will investigate the role of the AHOP2 gene in the model plant, Arabidopsis thaliana, to decipher how it functions in coordinating chromosome pairing and genetic exchange. We will examine whether AHOP2 undergoes chemical modifications that affect its function, and look for partner proteins that modulate its activities. The ahop2-1 mutant exhibits aberrant meiotic structures and we will strive to characterize the proteins that make up these structures. We also will characterize meiotic chromatin features for comparisons to those of the neighboring cell layer.     Chromosome pairing and genetic exchange are essential features of meiosis, the specialized form of nuclear division that uses these processes to ensure a balanced reduction of the chromosome number from diploid to haploid. The haploid meiotic products differentiate to produce the sperm and eggs that can participate in sexual reproduction. Reciprocal genetic exchange must be done precisely. Too little stringency results in inappropriate exchanges; too much stringency leads to inadequate numbers of exchanges; both scenarios lead to the production of genetically imbalanced chromosome sets.     Our team will consist of two Principal investigators, one 50%-time Research Associate, 3 graduate students and 6-8 undergraduates. Our research will utilize a broad range of microscopy and imaging, and genetic and molecular techniques to examine the function of AHOP2 in haploid and diploid plants. We also will use biochemical and genomic technologies to describe the chromatin remodeling associated with the transition from the vegetative to the meiotic program. The techniques and related skills we will utilize also are used in clinical, basic and applied research labs, as well as in industry. Students trained in our labs will be able to contribute to the knowledge and technology-driven sectors of the Canadian economy.      Meiosis is a critical process in the lifecycle of sexually reproducing organisms, and perturbations can lead to reduced fertility and birth defects. While chromosome movements during meiosis have long been documented, the molecular events that control pairing and ensure that exchange is done precisely are not yet fully understood. Our work should help identify molecular components of pairing and exchange and elucidate the role of AHOP2 in these processes. As well, our studies could enhance plant-breeding programs by allowing the stringency of exchange to be modulated to allow introgression of desirable genes into cultivated species from related wild species.     As meiosis is a conserved process, knowledge gained in the plants we study not only can contribute to agriculture, but also can contribute to a better understanding of the origins of birth defects in humans. Finally, many meiotic proteins also are essential to genome maintenance and repair; thus our research may lead to a deeper understanding of genome integrity and DNA repair.

我们将研究AHOP2基因在模式植物拟南芥中的作用，以破译它如何在协调染色体配对和遗传交换方面发挥作用。我们将检查AHOP2是否经历了影响其功能的化学修饰，并寻找调节其活动的伙伴蛋白。Ahop 2-1突变体表现出异常的减数分裂结构，我们将努力鉴定组成这些结构的蛋白质。我们还将描述减数分裂的染色质特征，以便与邻近细胞层的特征进行比较。 更多的染色体配对和遗传交换是减数分裂的基本特征，减数分裂是一种特殊的核分裂形式，它使用这些过程来确保染色体数量从二倍体平衡减少到单倍体。单倍体减数分裂产物分化产生参与有性繁殖的精子和卵子。互惠的基因交换必须准确地进行。太少的严格会导致不适当的交换；太严格会导致交换数量不足；这两种情况都会导致产生遗传不平衡的染色体集。 因此，我们的团队将由两名首席调查员、一名50%时间研究助理、3名研究生和6-8名本科生组成。我们的研究将利用广泛的显微镜和成像技术，以及遗传和分子技术来检测AHOP2在单倍体和二倍体植物中的功能。我们还将使用生化和基因组技术来描述与从营养细胞到减数分裂程序的转变相关的染色质重塑。我们将使用的技术和相关技能也用于临床、基础和应用研究实验室，以及工业中。在我们实验室接受培训的学生将能够为加拿大经济的知识和技术驱动型部门做出贡献。 减数分裂是有性繁殖生物体生命周期中的一个关键过程，扰动会导致生育力下降和出生缺陷。虽然减数分裂过程中的染色体运动早已被记录在案，但控制配对并确保准确完成交换的分子事件尚未完全了解。我们的工作应该有助于识别配对和交换的分子成分，并阐明AHOP2在这些过程中的作用。此外，我们的研究还可以通过调节交换的严格程度，允许将相关野生物种的可取基因导入栽培物种，从而加强植物育种计划。 由于减数分裂是一个保守的过程，从我们研究的植物中获得的知识不仅可以为农业做出贡献，还可以有助于更好地了解人类出生缺陷的起源。最后，许多减数分裂蛋白对基因组的维持和修复也是必不可少的，因此我们的研究可能会导致对基因组完整性和DNA修复的更深层次的了解。