ELUCIDATING the FUNDAMENTALS of BIOMOLECULAR TRANSPORT through NANOPORES

阐明通过纳米孔进行生物分子运输的基础知识

• 批准号: RGPIN-2016-05041
• 负责人: TabardCossa, Vincent
• 金额: $ 2.99万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708608
• 关键词: ELUCIDATING; FUNDAMENTALS; BIOMOLECULAR; TRANSPORT; through

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.

在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级孔隙的传输，是生命的基本过程。分子通过纳米孔转运的生物学例子包括mRNA通过核孔复合物；分泌：蛋白质穿过细胞膜的分泌；以及注射病毒DNA在体内，这种转运是通过与细胞膜和/或特定蛋白质的相互作用来主动控制的。阐明控制纳米孔传输现象的物理过程是一个丰富的研究领域，控制通道的策略将找到许多技术应用。