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

智力价值蛋白是所有细胞中的功能实体。它们是在称为核糖体的大分子机器上合成的。核糖体本身由78个蛋白质和4个RNA组成，组成大颗粒。细胞的功能依赖于核糖体将遗传密码中包含的信息准确地翻译成蛋白质。这反过来又需要核糖体的正确组装。实现正确的核糖体合成的一种方法是通过对步骤进行排序，以便后面的步骤依赖于先前步骤的准确性。该项目研究一种名为Bms1的调节蛋白质如何利用能量来调节和排序核糖体组装中的必要步骤。这些问题将在生化、动力学和遗传学实验的组合中得到解决。从这项工作中获得的见解也将对涉及RNA-蛋白质复合体的动态组装的其他细胞过程产生影响，包括前mRNA剪接和RNAi。更广泛的影响大型大学的教职员工在培养年轻科学家方面肩负着两项重要的、有时是相互竞争的使命。课堂教学的目的是向本科生和研究生传授已经建立起来的知识，而年轻的科学家则是在实验室中培养和教育的。密歇根大学的许多研究生对教师职业有着浓厚的兴趣，这使得通过培养也受过良好培训的教师的优秀科学家来将这两项使命联系起来变得重要。该项目的教育部分将开发一个名为科学发现的系列讲座。这一系列讲座将向本科生介绍尖端研究，既帮助他们在实验室和教科书之间建立联系，也激发他们对科学的兴趣。这一系列讲座是专门为让高级研究生和博士后参与本科生水平的教学而设计的(不仅仅是通过研究生导师的职位)。此外，生物化学实验课程中的新技术将介绍基于网络的酶学教学工具WebZyme。这种新颖的仪器将给学生提供机会，让他们进行他们通常不能做的实验，并向研究生导师介绍这一令人兴奋的新工具。预计虚拟酶学实验室在小型本科机构中可能特别有价值，许多学生认为这些机构是他们未来的理想雇主，从而提高他们的工作前景以及他们作为未来教师的有效性。

Intellectual MeritProteins are the functional entities in all cells. They are synthesized on large molecular machines, called ribosomes. Ribosomes themselves consist of 78 proteins and 4 RNAs, incorporated into large particles. Cellular function depends on ribosome accurately translating the information contained in the genetic code into proteins. This, in turn, requires the correct assembly of ribosomes. One way in which correct ribosome synthesis is achieved is by ordering steps, so that a later step depends on the prior steps being accurate. This project investigates how a regulatory protein, called Bms1, uses energy to regulate and order essential steps in ribosome assembly. These questions will be addressed in a combination of biochemical, kinetic and genetic experiments. Insights garnered from this work will also have implications for other cellular processes that involve the dynamic assembly of RNA-protein complexes, including pre-mRNA splicing and RNAi. Broader ImpactFaculty members at large universities have two important, sometimes competing, missions in educating young scientists. Class-room teaching is meant to convey already established knowledge to undergraduate and graduate students, while young scientists are raised and educated in the lab. Many graduate students at the University of Michigan have 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. The educational part of the project will develop a lecture series called Scientific Discovery. This lecture series will introduce undergraduate students to cutting edge research, both to help them make the connection between lab and textbook, but also to spark their interest in science. This lecture series is specifically designed to involve senior graduate students and postdocs in teaching at the undergraduate level (not just via Graduate Student Instructor positions). Furthermore, the new Techniques in Biochemistry Lab Course will introduce the web-based enzymology teaching tool webZyme. This novel instrument will give students the opportunity to "perform experiments" that they would normally not be able to do, and introduce the Graduate Student Instructor to this exciting new tool. It is expected that a virtual enzymology lab might be especially valuable in the small undergraduate institutions that many of our students have identified as their "ideal" future employers, thus enhancing their job prospects as well as their effectiveness as future teachers.