RUI: Elucidating Regulatory Mechanisms for Bridging the Contractile Ring with the Cellular Membrane in Fission Yeast Cytokinesis

智力优势。 细胞分裂是所有生物体生长和发育的基础。通过这项研究解决的广泛问题是所有生物系统中细胞分裂的普遍问题。一个单独的细胞如何知道在哪里物理分离成两个新的细胞？什么时候是细胞分裂的合适时间？对细胞物理分裂至关重要的蛋白质在细胞内经历动态重排，集中在未来的细胞分裂部位，并合并成一个称为收缩环的环状结构。当收缩环在胞质分裂期间收缩时，母细胞物理分离成两个相同的细胞。要在细胞分裂位点组织如此大量的蛋白质，需要精确的调控机制。由于裂殖酵母（裂殖酵母）细胞在此过程中利用进化保守的机制，它们是揭示一般细胞分裂特性的理想模型系统。在分裂酵母中，一种称为Mid 1的保守支架蛋白是收缩环的基础部分，作为最初的组织者将结构锚在细胞膜上，并将必需的细胞动力学蛋白募集到细胞分裂位点。在这个项目中，一个主要由本科生组成的研究小组将在分子水平上研究Mid 1支架功能。学生研究人员产生的初步结果表明，Mid 1直接与多种细胞动力学环蛋白相关，并利用酶依赖性机制与细胞膜相互作用。这项研究将描述Mid 1与其他细胞动力学蛋白和细胞膜的相互作用，以阐明将细胞分裂机制与细胞膜连接起来的分子模型。鉴于Mid 1在功能上类似于动物细胞胞质分裂所需的支架蛋白苯胺醛，因此对Mid 1支架功能的详细研究是理解其他生物系统胞质分裂的核心。在大峡谷州立大学（GVSU）的20，000多名本科生中，41%的新生是家庭中第一个上大学的，15.5%的应届毕业生年龄超过25岁（非传统），大多数在校学生都在为自己的教育做出经济贡献。和GVSU的许多学生一样，首席研究员自己也是第一代大学毕业生。这个研究项目的一个具体目标是提供一个智力上有意义的研究经验，本科生，主要是第一代学生和/或非传统的学生。学生研究人员将有助于与细胞分裂相关的科学目标，同时接受全面的培训经验。获得的实践技能将包括创造性地解决问题，适当的实验室技术，清晰的口头和书面沟通，假设发展和实验设计。研究结果将在同行评审的期刊上发布，本科研究人员将在区域和国家科学会议上展示他们的研究结果。GVSU的细胞和分子生物学专业在全国名列前茅，在这一领域的标准化考试中一直得分很高。毕业生在博士课程或工业研究岗位上做出重大科学贡献。该研究项目的教育目标将对致力于长期科学事业的学生产生积极影响，并将进一步加强GVSU的研究氛围。

Intellectual Merit. Cell division is a fundamental biological event that underlies the growth and development of all organisms. The broad questions addressed through this research are universal to cell division in all biological systems. How does an individual cell know where to physically separate into two new cells? When is an appropriate time for a cell to divide? Proteins that are essential for physically dividing the cell undergo dynamic rearrangements within the cell to concentrate at the future site of cell division and coalesce into a ring structure called the contractile ring. Physical separation of the mother cell into two identical cells occurs when the contractile ring constricts during cytokinesis. Temporally and spatially organizing such a large assortment of proteins at the cellular division site requires precise regulatory mechanisms. Because fission yeast (Schizosaccharomyces pombe) cells utilize evolutionarily conserved machinery during this process, they are an ideal model system to reveal general cell division properties. In fission yeast, a conserved scaffolding protein called Mid1 is a foundational part of the contractile ring, functioning as the initial organizer to anchor the structure to the cell membrane and to recruit essential cytokinetic proteins to the cell division site. In this project, a research team, consisting primarily of undergraduate students, will investigate the Mid1 scaffolding function at a molecular level. Preliminary results generated by student researchers suggest that Mid1 directly associates with multiple cytokinetic ring proteins and utilizes an enzyme-dependent mechanism to interact with the cell membrane. The research will characterize Mid1 interactions with other cytokinetic proteins and the cell membrane to elucidate a molecular model for bridging the cell division machinery to the cell membrane. Given that Mid1 is functionally similar to anillin, a scaffolding protein required for cytokinesis in animal cells, a detailed study of the Mid1 scaffolding function is at the core of understanding cytokinesis in other biological systems.Broader Impact. Among the greater than 20,000 undergraduate students at Grand Valley State University (GVSU), 41% of incoming freshman are the first in their family to attend college, 15.5% of recent graduates were over the age of 25 years (non-traditional) and the majority of current students are financially contributing to their own education. Like many of the students at GVSU, the principal investigator is a first-generation college graduate herself. A specific objective of this research project is to provide an intellectually meaningful research experience to undergraduate students, primarily first generation students and/or non-traditional students. Student researchers will contribute to the scientific goals related to cell division while receiving a comprehensive training experience. The practical skills gained will include creative problem solving, proper laboratory technique, clear oral and written communication, hypothesis development, and experimental design. Results will be disseminated in peer-reviewed journals, and undergraduate researchers will present their findings at regional and national scientific meetings. Cell and molecular biology majors at GVSU are among the top in the country with consistently high scores on standardized tests in this area. Graduates are making significant scientific contributions in doctoral programs or industrial research positions. The educational goals of this research project will positively impact students who are committed to long-term scientific careers and will further intensify the research atmosphere at GVSU.