2023 Sam Edwards Medal and Prize

The transport of nucleic acid molecules through holes in membranes is a ubiquitous process, crucial in biology, medicine and many technological applications. To understand and exploit the underlying physical principles that are still largely unexplored at the single-molecule level, Professor Ulrich Keyser has built on his early breakthroughs in combining optical tweezers with solid-state nanopores and pioneered the use of DNA nanotechnology for the quantification of polymer dynamics in nanopores. Over the past decade, he has designed and constructed uniquely structured DNA molecules that allow for controlling the translocation of macromolecules in aqueous environments at room temperature with nanometre spatial resolution.

Key steps in these remarkable developments have been the systematic design of linear polymers with sophisticated patterns that can be deciphered by nanopore sensing. The design of these nucleic acid-based polymers enables unprecedented experiments on polymer transport. Keyser uses solid-state nanopores to directly measure the instantaneous velocity during DNA transport dynamically, directly testing existing theories on polymer translocation. His quantitative understanding of the physics of the translocation process allows for the precise localization of binding sites along nucleic acid molecules approaching single-nanometre precision rivalling super-resolution microscopy. Building on this, he used nucleic acid self-assembly to distinguish different RNA molecules by analysing designed patterns. The creation of structural labels made from RNA or DNA avoids the usually necessary fluorophores for molecular identification. During the Covid-19 pandemic, the nanopores sensing scheme was adapted to allow for the multiplexed identification of pathogens able to distinguish viruses and their variants. This technology has advanced rapidly from genesis to practical implementation. Remarkably, it is now able to be used in the field for rapid pathogen detection, and is due to be trialled in East Africa.

In parallel, the rapid nanopore readout of the structured DNA is the basis for a novel approach for DNA data storage and computation. Keyser designs experiments that reveal the main forces of interaction during translocation. His multidisciplinary approach has generated many fruitful partnerships leading to striking advances in sensing the presence and interactions of significant biomolecules. He focuses on rigorous quantitative data, developing a deeper understanding and then translating his findings into application that rely on molecular control of macromolecular transport. The development of unique single-molecule techniques has allowed him to demonstrate remarkable progress in the past decade, transforming the understanding of molecular forces in aqueous environments and enhancing our understanding of out-of-equilibrium polymer physics.