RUI: Chromosome organization in cellular development

该项目的目标是揭示人类细胞在细胞分裂过程中如何调节其染色体组织。在细胞分裂过程中，染色体将复制并在两个子细胞中平均分裂。在人类细胞分裂期间发生的染色体分离异常可导致有害后果和疾病。该项目支持一个西班牙裔服务机构的研究小组，致力于了解染色体组织的基本原理。它还为生命科学领域代表性不足的学生群体的招聘和入学提供了坚实的基础。参与生命科学研究的机会也将提供给当地社区的多个人群，包括社区大学和高中学生以及成年老年人，以促进STEM领域的多样性和公平。有丝分裂中的同源染色体配对可导致人类体细胞中等位基因的错误调节和基因组的不稳定性。在胚胎发生和成年期的整个细胞周期中，同源染色体配对是如何被阻止的，目前还知之甚少。该研究项目将探索这种基本上未受影响的生物学范式。实验计划专门测试一个单倍体组与另一个的区室化是否在间期保守，从而在整个细胞周期中保守。两种类型的孤雌生殖细胞将被用来进一步确定这种区室化是否取决于父母起源的着丝粒。这项全面的研究将产生新的机制信息，以前未被识别的单倍体集为基础的染色体组织。此外，它将首次揭示细胞周期中高阶染色体组织的潜在分子机制。这些结果应该开辟了一条新的途径，探索高阶染色体组织在发育中的重要性，这对于阐明细胞功能的新机制至关重要。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

The goal of this project is to uncover how human cells regulate their chromosome organization during cell division. During cell division, chromosomes will duplicate and divide equally among two daughter cells. Abnormalities in chromosome segregation that occur during cell division in humans can lead to detrimental consequences and disease. This project supports a research group in a Hispanic serving institution dedicated to understanding the fundamental principles of chromosome organization. It also provides a strong foundation for recruitment and accessibility of under-represented student populations in the life sciences. Opportunities for engagement with life science research will also be made available to multiple populations in the local community, including community college and high school students as well as adult seniors, in order to promote diversity and equity in STEM fields. Homologous chromosome pairing in mitosis can lead to allelic mis-regulation and genome instability in human somatic cells. Little is known about how homologous chromosome pairing is prevented throughout the cell cycle during embryogenesis and adulthood. The research project will explore this largely untouched biological paradigm. Experiments are planned to specifically test whether compartmentalization of one haploid set from the other is conserved at interphase, and thus throughout the cell cycle. Two types of parthenogenic cells will be used to further determine if this compartmentalization depends on the parental origin of the centromere. This comprehensive study will generate new mechanistic information of the previously unrecognized haploid set-based chromosome organization. Further, it will reveal, for the first time, the underlying molecular mechanisms for higher-order chromosome organization during the cell cycle. These results should open up a new avenue to explore the importance of higher-order chromosome organization in development that will be critically important for elucidating new mechanisms of cellular function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.