Dynamics of the Nuclear Pore Proteins and the Mechanism of Transport

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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.