Understanding the mechanisms of biological transport and signaling for nanotechnology applications

为了发挥功能，活细胞需要将各种分子输送进和运出细胞，以及在不同的细胞室之间运输。大自然进化出了这种受控运输的装置和机制，将精致的选择性、敏感性和吞吐量与针对结构破坏和环境噪声的高度稳健性结合在一起。一些转运蛋白，如离子通道，已经被研究了几十年。其他的功能机制，如那些将蛋白质运入和运出细胞核，或参与细菌蛋白质分泌的机制，仍然不完全清楚。了解这种生物转运蛋白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，这种生物机器是设计人造设备的灵感来源，这些设备可以用于各种应用--从药物输送到病原体检测。这种生物和人工渠道的功能提出了几个基本的生物和物理问题。选择性机制是什么(这些通道如何区分有时相似的分子，一个需要通过，另一个必须过滤)？它们如何获得敏感度(从其他分子的海洋中‘挑选’出一个必要的分子的能力)？为了解决这些和许多其他问题，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；它们提供不同假设的严格结论，然后可以在额外的实验中验证或反驳这些结论。数学建模也是一个强大的“显微镜”，它允许访问不能通过实验直接测量的过程。我的研究将集中在统计物理学在几个特定生物运输系统的研究中的应用，目的是了解它们在医学和纳米技术中应用的功能的基本原理。

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.