ELUCIDATING the FUNDAMENTALS of BIOMOLECULAR TRANSPORT through NANOPORES

受限几何结构中的动态现象，包括带电生物聚合物通过纳米尺度的孔的传输，是生命的基本过程。通过纳米孔进行分子移位的生物学例子包括：mRNA通过核孔复合体；蛋白质跨细胞膜分泌；以及从病毒中注入DNA。在体内，这种转运受到与细胞膜和/或特定蛋白质的相互作用的积极控制。阐明支配纳米孔传输现象的物理过程是一个肥沃的研究领域，控制通道的策略将发现许多技术应用。*在过去十年中，纳米流体设备在开发仿生系统和研究单分子水平的运输过程方面取得了重大进展。特别是，通过研究核酸通过固态纳米孔(SSNP)，已经取得了令人振奋的结果。SSNP是薄介质膜上的纳米大小的孔，已经成为研究涉及DNA和蛋白质的广泛现象的一种通用工具。基本概念依赖于监测离子电流的变化，以提供有关转移分子的物理和化学信息。除了DNA测序，这一概念还显示出巨大的应用前景，包括分子计数、扫描DNA分子的局部结构或研究单生物分子之间的相互作用。然而，当前SSNP设备有限的时空分辨率和/或捕获效率阻碍了这些在现实世界应用中的实现。通过更深入地了解通过SSNP转移聚合物的动力学，将出现克服这些限制的创新解决方案。为此，这项研究计划将集中于通过实验阐明支配通过纳米孔的生物分子运输现象的物理过程的长期目标。其目标将是开发新的策略或设备，以获得对捕获速度的控制和在飞行过程中操纵分子运动，并最终将这些发现转化为新的工具，以表征单分子过程和研究生命的基本过程。*在这项为期5年的计划过程中产生的新知识可能会确保加拿大生物医药行业在固态纳米孔技术开发方面获得全球竞争优势。此外，该项目还将在一系列尖端单分子技术方面为高素质人才(HQP)提供有价值的多学科培训。这些技能将使HQP能够满足我们不断增长的高科技行业的需求，从而加强加拿大以知识为基础的经济，并确保其研究投资获得最大回报。

Dynamic phenomena in confined geometries, including the transport of charged biopolymers through nanoscale pores, are fundamental processes of life. Biological examples of molecular translocation through nanopores include the passage of mRNA through the nuclear pore complex; the secretion of proteins across cell membranes; and the injection of DNA from viruses. In vivo, such transport is actively controlled by interactions with cellular membranes and/or specific proteins. Elucidating the physical processes that govern nanopore transport phenomena is a fertile field of research, and strategies for controlling passage will find numerous technological applications. ******The last decade has seen significant advancements in nanofluidic devices to develop biomimetic systems and to study transport processes at the single-molecule level. In particular, exciting results have been obtained through the study of passage of nucleic acids through solid-state nanopores (ssNP). ssNP are nanometer-sized holes in thin dielectric membranes, which have emerged as a versatile tool to investigate a wide range of phenomena involving DNA and proteins. The basic concept relies on monitoring ionic current changes to provide physical and chemical information about the translocating molecule. In addition to DNA sequencing, this concept exhibits great promise for other applications, including molecular counting; scanning of local structures along DNA molecules, or the investigation of single biomolecular interactions. However, the limited spatiotemporal resolution and/or capture efficiency of current ssNP devices hinder these implementation for real-world applications. Innovative solutions to overcome these limitations will emerge from a deeper understanding of the dynamics of translocation of polymers through ssNP. To this end, this research program will be focused on the long-term objective of experimentally elucidating the physical processes governing biomolecular transport phenomena through nanopores. The goal will be to develop novel strategies or devices for gaining control over capture rate and manipulating molecular motion during passage and, ultimately, to translate these discoveries into new tools to characterize single-molecule processes and to study fundamental processes of life. ******The new knowledge generated over the course of this 5-year program could potentially secure a global competitive edge for Canada biomedical industry in the development of solid-state nanopore technologies. In addition, this program will offer valuable multidisciplinary training to highly qualified personnel (HQP) in a range of cutting-edge single-molecule techniques. These skills would position HQP to meet the demands of our growing high-tech industry, thereby strengthening Canada's knowledge-based economy and ensuring maximum return from its research investments.**