Dynamics of the Nuclear Pore Proteins and the Mechanism of Transport

知识价值。在细胞中发现的纳米级分子机器在复杂性上超过了人类创造的任何东西，在效率上也大大超过了人类创造的任何东西。它们负责细胞功能，从跨膜运输物体到合成机器，再到将货物从一个地方运送到另一个地方的马达。对于一些较小的机器，我们已经能够将我们对这些机器结构的研究与我们对机器工作的观察结合起来，从而为机器如何工作提供见解。唉，我们分析和理解更大、更复杂的生物机器的能力。这个项目开发计算工具来测试这些机器是如何工作的。第一个要研究的模型是调节细胞核内外运输的孔，核包膜是细胞的中心部分，保护着我们的基因组。初步研究表明，计算的进步可以让我们理解这些机器是如何在分子水平上以如此高的效率和速度运行的。更广泛的影响。这些结果在几个重要层面上产生了影响。首先，了解保护细胞核的毛孔的基本运作是细胞生物学的一个重要目标。哪些基因被打开或关闭通常取决于哪些分子被允许通过细胞核周围的这些孔进入。其次，我们需要充分了解这些毛孔的故障如何影响细胞的正常状态和完整性。第三，纳米级细胞机器所使用的工程设计原理的实际应用，在应用和扩展到其他问题时，可以具有巨大的经济和技术潜力。大自然创造的纳米机器在效率上远远超过人类创造的任何东西。了解这些纳米机器的工作原理可以为我们自己的技术提供见解。第四，这项工作使科学研究能够为更广泛的群体所接受。调查人员已经在纽约公立学校系统工作了35年。目前的工作包括在夏季将高中教师和他们的学生整合到实验室中，作为纽约科学院教育委员会的董事会成员参加，为纽约地区的科学教师组织每月的会议，以及在纽约地区的初中和高中安排研究生和博士后。尽管大多数高中生没有机会接触到高端的实验工具，但这样的工作可以在家用个人电脑上完成，从而使这门科学能够为广大人群所接受，否则他们可能没有机会从事科学研究。

Intellectual merit. Nanoscale molecular machines found in a cell exceed any human creations in their intricacy and vastly exceed anything humans have created for efficiency. These are responsible for cellular functions that range from transporting objects across membranes to machines that synthesize, to motors that move cargo from one location to another. For a few of the smaller machines we have been able to merge our studies on the structure of these machines, with our observations on what the machine is doing and, as result, provide insight to how the machine works. Alas, our ability to analyze, and therefore understand, the larger, more sophistical biological machines. This project develops the computational tools to test how these machines work. The first model to be studied is the pore that regulates transport in and out of the nucleus across the nuclear envelope, the central part of the cell that guards our genome. Preliminary studies demonstrate that advances in computation can allow us to understand how these machines function at a molecular level with such great efficiency and speed. Broader impacts. These results have impacts on several important levels. First, understanding the basic operation of the pores that guard the nucleus is an essential goal of cell biology. Which genes are turned on and off often depends upon which molecules are allowed to enter through these pores that surround the nucleus. Second, we need to fully understand how malfunctions of these pores can affect the normal state and integrity of the cell. Third, practical application of the engineering design principles used by cellular machines at a nanoscale can have tremendous economic and technological potential when applied and scaled to other problems. Nature has created nanomachines that vastly exceed in efficiency anything humans have created. Understanding how these nanomachines work can provide insights into our own technology. Fourth, this work makes science research accessible to a much broader community. The investigators have been working in the New York public school system for 35 years. Current involvement includes integrating high school teachers and their students in the laboratory over the summer, participating as a board member of the education committee of the New York Academy of Sciences, running monthly meetings for New York regional science teachers, as well as placing graduate students and postdoctoral fellows in middle and high schools in the New York area. Even though most high school students do not have access to high-end experimental tools, work such as this can be done on a home personal computer, thus making this science accessible to a broad population, which might not otherwise have the chance to pursue scientific research.