CAREER: Dissecting the Regulation of Ribosome Assembly by the Essential GTPase Bms1

蛋白质分子是所有活细胞中重要的功能实体。它们是由核糖体以模板导向的方式合成的，核糖体是由78种蛋白质和4种RNA组成的大分子机器。由于每种蛋白质的合成取决于核糖体翻译其相应mRNA模板中编码的遗传信息的能力，因此蛋白质合成的准确性反过来取决于核糖体从其组成蛋白质和RNA组分的正确组装。实现正确的核糖体合成的一种方法是通过对组装步骤进行排序，使得后一步骤仅在前一步骤已经准确地进行之后进行。该项目的重点是阐明一种称为Bms 1的调节蛋白利用GTP的能量调节和命令核糖体组装中的重要步骤的机制。这些问题将解决实验使用的生物化学，动力学和遗传方法的组合。从这项工作中获得的预期见解将对涉及大RNA-蛋白质复合物的其他动态细胞组装过程产生影响，包括参与前mRNA剪接或涉及小RNA的基因调控的过程，称为RNA干扰（RNAi）。 更广泛的影响年轻科学家的教育需要两个平行的轨道：课堂教学的目的是有效地传达既定的知识，本科生和研究生，而适当设计的实验室经验介绍年轻科学家的实际科学实践。许多PI？美国的研究生和博士后都对教学职业表示了浓厚的兴趣，因此通过培养优秀的科学家来将这两项任务联系起来非常重要，这些科学家也受过良好的教师培训。为了实现这一目标，PI在她的第一个18个月的资金建立了一个生物化学入门实验室，现在是生物化学学士学位核心课程的一部分。在密歇根大学获得学位。跟踪PI？她搬到了佛罗里达的斯克里普斯研究所，继续通过两个主要的推动力，补充斯克里普斯研究生课程与本科生和其他年轻科学家建立关系。斯克里普斯佛罗里达有一个强大的社区外展计划，高中学生和教师在暑假期间加入斯克里普斯实验室，体验科学（学生）或更新他们的技能和知识（高中教师）。PI参与了该计划。此外，斯克里普斯有一个不断增长的计划，以支持优秀的本科生（许多来自少数民族背景）进行暑期研究实习，最终目标是促进科学事业。PI通过招募学生并接受他们加入她的研究小组来参与该计划。

Intellectual MeritProtein molecules are important functional entities in all living cells. They are synthesized in a template-directed manner by ribosomes, large macro-molecular machines that themselves are composed of 78 proteins and 4 RNAs. As the synthesis of each protein depends on the ability of ribosomes to translate the genetic information encoded in its corresponding mRNA template, the accuracy of protein synthesis is in turn dependent on the correct assembly of ribosomes from their constituent protein and RNA components. One way by which correct ribosome synthesis is achieved is by ordering the assembly steps, so that a later step proceeds only after a prior step has been carried out accurately. The focus of this project is to elucidate the mechanism by which a regulatory protein called Bms1 regulates and orders essential steps in ribosome assembly, using the energy of GTP. These questions will be addressed experimentally using a combination of biochemical, kinetic and genetic approaches. Anticipated insights obtained from this work will have implications for other dynamic cellular assembly processes involving large RNA-protein complexes, including those participating in pre-mRNA splicing or in gene regulation involving small RNAs, known as RNA interference (RNAi). Broader ImpactThe education of young scientists requires two parallel tracks: Class-room teaching is intended to efficiently convey established knowledge to undergraduate and graduate students, while appropriately designed laboratory experiences introduce young scientists to the actual practice of science. Many of the PI?s graduate students and postdocs have expressed a strong interest in teaching careers, which makes it important to connect these two missions by raising excellent scientists that are also well-trained as teachers. Towards this goal, the PI has established in her first 18 months of funding an Introductory Laboratory in Biochemistry, which is now part of the core curriculum in the Biochemistry B.S. degree at the University of Michigan. Following the PI?s move to The Scripps Research Institute in Florida, she continues to build relationships with undergraduate students and other young scientists via two main thrusts that complement the Scripps graduate program. Scripps Florida has a strong community outreach program, whereby High School students and teachers join Scripps labs over the summer break to get a taste of science (in the case of students) or to have their skills and knowledge updated (in the case of high school teachers). The PI participates in this program. Furthermore, Scripps has a growing program to support excellent undergraduates (many from minority backgrounds) to conduct summer research internships with the end goal of promoting careers in science. The PI participates in this program by recruiting students and accepting them in her research group.