Understanding the mechanisms of biological transport and signaling for nanotechnology applications

为了发挥功能，活细胞需要运输各种分子进出细胞，以及在不同的细胞区室之间运输。大自然已经进化出了这种受控传输的设备和机制，将精致的选择性、灵敏度和吞吐量与结构损坏和环境噪声方面的高稳健性结合起来。一些转运体，如离子通道，已经被研究了几十年。其他的功能机制，如将蛋白质运送进出细胞核，或参与细菌的蛋白质分泌，仍未完全了解。了解这些生物转运体的工作原理不仅是一个重要的生物学问题，而且在疾病治疗中也有重要的应用。此外，这种生物机器为设计可用于从药物输送到病原体检测等各种应用的人工设备提供了灵感。这种生物和人工通道的功能提出了几个基本的生物学和物理学问题。什么是选择性机制（这些通道如何区分有时相似的分子，一个需要通过，另一个必须被过滤掉）？它们如何实现灵敏度（从众多分子中“挑选”必要分子的能力）？为了解决这些问题和许多其他问题，为了阐明基本的一般原理，实验工作必须与计算和数学建模相结合。数学模型是对数据进行系统分析的工具；它们为不同的假设提供了严谨的结论，然后这些结论可以在额外的实验中得到证实或证伪。数学建模也可以作为一个强大的“显微镜”，允许访问的过程，不能直接测量实验。我的研究将集中在统计物理学在几种特定生物传输系统的研究中的应用，目的是利用对其功能的基本原理的理解，将其应用于医学和纳米技术。

In order to function, living cells need to transport various molecules into and out of the cell, as well as between different cellular compartments. Nature has evolved devices and mechanisms for this controlled transport that combine exquisite selectivity, sensitivity and throughput with high robustness with respect to structural damage and environmental noise. Some transporters, such as ion channels, have been studied for decades. The mechanisms of function of others, such as those transporting proteins into and out of the cell nucleus, or involved in protein secretion by bacteria, are still not fully understood. Understanding the principles of operation of such biological transporters is not only an important biological question, but it also has important applications in disease treatment. Moreover, such biological machines serve as an inspiration for the design of artificial devices that can be used in a variety of applications - from drug delivery to pathogen detection. The functioning of such biological and artificial channels poses several fundamental biological and physical questions. What is the selectivity mechanism (how do these channels discriminate between the sometimes similar molecules, one that needs to pass, and another that has to be filtered out)? How do they achieve sensitivity (ability to 'pick' a necessary molecule from the sea of others)? In order to resolve these and many other issues and in order to elucidate the basic general principles, the experimental work has to be coupled to computational and mathematical modeling. Mathematical models are a tool for systematic analysis of the data; they provide rigorous conclusions of different hypotheses that then can be verified or disproven in additional experiments. Mathematical modeling also serves as a powerful 'microscope' that allows to access processes that cannot be directly measured experimentally. My research will focus on the application of the statistical physics to the investigation of several specific biological transport systems, with the goal of leveraging the understanding of the basic principles of their function for applications in medicine and nanotechnology.