INMA seminar: Ulrich F. Keyser, from the Cavendish Laboratoryt, University of Cambridge (UK)
Date: Thu 18th Sep. 2025 16:00
Venue: Aula, Edificio I+D+i, Campus Río Ebro
Ulrich F. Keyser, from the Cavendish Laboratory, University of Cambridge (UK): “Native RNA detection using nanopores: isoforms, RNA modifications and disease diagnostics”
Abstract: Rapid identification of RNA molecules is a major challenge in biotechnology. This is driven by the discovery of RNAs that control cellular function ranging in length from a few to 1000s of nucleotides. Here we design three dimensional nucleic acid constructs that enable the identification of short and long RNA molecules and nanopore readout. [1] First, we describe the identification of long transcript isoforms at the single-molecule level using solid-state nanopore microscopy. We refold target RNA into RNA identifiers (IDs) with designed sets of complementary DNA strands. Each reshaped molecule carries a unique sequence of structural (pseudo)colours. The sequence of structural colours of RNA identifiers enables simultaneous identification and relative quantification of multiple RNA targets without prior amplification. RNA IDs discriminate circular and linear transcript isoforms in a one-step, enzyme-free reaction in a complex human transcriptome using single-molecule read-out [1]. We will show recent results on detection of RNA modifications like 5mC, Inosine and MeC using RNA nanotechnology in ribosomal RNA (rRNA) from pathogenic bacteria like A. baumannii [2] using loop formation in RNA and DNA.[3]
References:
1. F. Bošković and U. F. Keyser. Nanopore microscope identifies RNA isoforms with structural colors. Nature Chemistry, 14:1258-1264, 2022.
2. Y. Li, S. C. Meng, Y. Wang, C. M. Platnich, M. K. Earle, E. Mylona, P. Naydenova, S. Baker, J. Zhu and U. F. Keyser. Nanopore detection of single-nucleotide RNA mutations and modifications with programmable nanolatches. Nature Nanotechnology, published online, 2025. https://doi.org/10.1038/s41565-025-01965-6
3. J. Zhu, J. , R. Tivony, F. Bošković, J Pereira-Dias, S. E. Sandler, S. Baker, and U. F. Keyser. Multiplexed Nanopore-Based Nucleic Acid Sensing and Bacterial Identification Using DNA Dumbbell Nanoswitches. JACS, 145:22, 12115–12123, 2023
