Dynamics of the Nuclear Pore Proteins and the Mechanism of Transport

智力上的优点。在细胞中发现的纳米级分子机器在复杂性上超过了任何人类创造的东西，也远远超过了人类为提高效率而创造的任何东西。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对机器运行情况的观察结合在一起，从而为机器如何工作提供了洞察力。唉，我们分析并理解更大、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。要研究的第一个模型是调节穿过核膜进出细胞核的毛孔，核膜是保护我们基因组的细胞的中心部分。初步研究表明，计算的进步可以让我们了解这些机器如何在分子水平上以如此高的效率和速度发挥作用。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，了解保卫细胞核的毛孔的基本运作是细胞生物学的基本目标。哪些基因的开启和关闭通常取决于哪些分子被允许通过这些围绕细胞核的小孔进入。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，细胞机器在纳米尺度上使用的工程设计原理的实际应用，如果应用于其他问题并扩展到其他问题，将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。了解这些纳米机器是如何工作的，可以为我们自己的技术提供见解。第四，这项工作使更广泛的社区能够接触到科学研究。调查人员已经在纽约公立学校系统工作了35年。目前的参与包括在夏季将高中教师和他们的学生纳入实验室，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举办每月会议，以及将研究生和博士后研究员安排在纽约地区的初中和高中。尽管大多数高中生无法获得高端实验工具，但这样的工作可以在家用个人电脑上完成，从而使广大人口能够接触到这门科学，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.