Mechanisms and Regulation of Cell Division

细胞分裂是一组高度协调的事件，确保遗传物质从一个母细胞忠实地传递到两个新形成的子细胞。有丝分裂纺锤体是细胞用来分离遗传物质的复杂分子机器。然而，有丝分裂装置的组装和调控仍然不完全清楚。这个项目将通过阐明五种酶在有丝分裂中的作用和功能机制来增加这种理解，这些酶在有丝分裂中的作用以前还没有被认识到。该项目将通过培训和准备下一代科学家在STEM领域的职业生涯，对社会产生更广泛的影响。不同层次的学生，从高中到研究生，将参加教育、指导和研究培训活动。这项研究将使学生能够成为独立的批判性思考者，产生科学数据，并开发免费提供并将造福于科学界的计算软件。所有研究成果将通过出版物、研究报告和科学推广活动向广大受众传播。有丝分裂纺锤体主要由微管组成，是细胞分裂过程中的关键。它的正确组装、功能和调节依赖于大量的酶反应和蛋白质-蛋白质相互作用，这些反应和相互作用在空间和时间上受到严格控制。目前将细胞分裂理解为生物系统的努力由于缺乏对促进细胞分裂的酶机制及其机制功能的了解而受到阻碍。这一提议以协同的方式整合了实验和计算方法，以弥补这些知识上的差距。最近在蛋白质组筛选中发现了许多在细胞分裂中具有未知作用的酶，以鉴定新的有丝分裂微管相关蛋白。基因筛查证实了这些蛋白质对细胞分裂的重要性。这些被命名为新的细胞分裂蛋白(NCDPs)。为了进一步阐明驱动和调控细胞分裂的机制，本项目将利用一系列细胞生物学、分子、遗传和生化方法来表征五个NCDP的功能，以确定它们在细胞分裂中的定位、功能和调节模式。该项目将开发新的计算工具来分析NCDP蛋白质组数据集，并建立一个用户友好的开放访问网络服务器，科学界可以使用它来分析质谱学数据。总之，这项研究将促进对驱动和调节细胞分裂的酶活动的理解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Cell division is a highly coordinated set of events that ensures the faithful transmission of genetic material from one mother cell to two newly formed daughter cells. The mitotic spindle is the complex molecular machine used by the cell to separate the genetic material. However, the assembly and regulation of the mitotic apparatus is still incompletely understood. This project will increase this understanding by elucidating the role and mechanism of function of five enzymes whose roles in mitosis have not been previously appreciated. This project will have a Broader Impact for society by training and preparing the next generation of scientists for careers in STEM fields. A diverse group of students at all levels, from high school through graduate students, will participate in educational, mentoring, and research training activities. This research will enable students to become independent critical thinkers, to generate scientific data, and to develop computational software that will be freely available and will benefit the scientific community. All research results will be disseminated to a broad audience through publications, research presentations, and at science outreach events. The mitotic spindle, comprised largely of microtubules, is key to the process of cell division. It's proper assembly, function, and regulation relies on a multitude of enzymatic reactions and protein-protein interactions that are tightly controlled in a spatial and temporal manner. Current efforts to comprehend cell division as a biological system have been hampered by a lack of understanding of the enzymatic machinery and their mechanistic functions that contribute to cell division. This proposal integrates experimental and computational approaches in a synergistic fashion to address these gaps in knowledge. Many enzymes with uncharacterized roles in cell division were recently uncovered in a proteomic screen to identify novel mitotic microtubule associated proteins. Genetic screens confirmed the importance of these proteins for cell division. These were termed novel cell division proteins (NCDPs). To further elucidate the mechanisms that drive and regulate cell division, this project will characterize the function of five NCDPs using a range of cell biological, molecular, and genetic, and biochemical approaches to determine their localization, function and mode of regulation in cell division. This project will develop novel computational tools to analyze NCDP proteomic data sets, and establish a user-friendly open access web server that the scientific community can use to analyze mass spectrometry data. Together, this research will advance an understanding of the enzymatic activities that drive and regulate cell division.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.