ELUCIDATING the FUNDAMENTALS of BIOMOLECULAR TRANSPORT through NANOPORES

点击翻译按钮获取中文摘要

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.