Regulation of the anaphase-promoting complex by pseudosubstrate inhibition

研究项目描述。细胞分裂的过程，即一个亲本细胞产生两个相同的子细胞，是惊人的复杂。其核心是细胞整个基因组的复制，以及基因组的一个完整拷贝准确地分配给两个子细胞中的每一个。值得注意的是，几乎所有的非细菌物种都使用相同的基本机制和调节控制来实现细胞分裂。细胞分裂中涉及的复杂步骤是如何调节的，仍然只是部分了解。在这个项目中，芽殖酵母将被用作一个简单的模型系统来研究细胞分裂控制的一个重要组成部分，调节蛋白质破坏。该项目旨在了解细胞分裂过程中负责蛋白质破坏的关键酶如何被激活和失活，以及它特异性识别其靶点的机制。通过使用酵母模型系统，跨越细胞生物学、遗传学、生物化学和生物物理学领域的广泛的分子技术将被应用于实现目标。该项目将有助于推进对1）细胞分裂控制和2）受调控的蛋白质破坏的分子机制的一般理解。该研究项目与生物化学的研究生和本科生课程有关。一个主要重点是教育和培养学生的批判性思维和科学方法，作为独立研究科学家的未来职业的基本技能和任何科学相关职业的重要技能。第二个重点是在广泛的基础分子生物学技术的研究技能的发展，这将为学生准备各种研究相关的职业生涯。最后，第三个目标是发展有效的科学沟通技能。这一目标的最终结果是学生在国家科学会议上介绍研究成果，并在同行评审的科学期刊上发表研究论文。总之，该项目将有助于培养下一代研究科学家，并有助于公众收集基本生物学知识。

Research Project Description. The process of cell division, by which a single parent cell gives rise to two identical daughter cells, is amazingly complex. At its core are the duplication of the cell's entire genome and the accurate distribution of one intact copy of the genome to each of the two daughter cells. Remarkably, almost all non-bacterial species use the same basic machinery and regulatory controls to achieve cell division. How the complex steps involved in cell division are regulated is still only partially understood. In this project, budding yeast will be used as a simple model system to study one essential component of cell division control, regulated protein destruction. The project aims to understand how a key enzyme responsible for protein destruction during cell division is activated and inactivated, and the mechanism by which it specifically recognizes its targets. By using the yeast model system, a broad array of molecular techniques spanning the fields of cell biology, genetics, biochemistry, and biophysics will be applied to achieve the aims. The project will help advance the general understanding of molecular mechanisms of 1) cell division control, and 2) regulated protein destruction.Broader Impact. The research project is associated with graduate and undergraduate programs in biochemistry. A major focus is education and training of students in critical thinking and the scientific method, essential skills for future careers as independent research scientists and important skills for any science-related career. A secondary focus is development of research skills in a broad array of fundamental molecular biological techniques that will prepare students for a variety of research-related careers. Finally, a third goal is development of effective scientific communication skills. The culmination of this goal is presentation of research results at national scientific meetings by students and publication of research papers in peer-reviewed scientific journals. In summary, this project will help train the next generation of research scientists and contribute to the public collection of basic biological knowledge.