Technique to analyze RNA structures in ultra-high definition

The OrbiSIMS
Credit: The University of Nottingham

This is where the Nottingham team, led by Dr Aditi Borkar, Assistant Professor in Molecular Biochemistry & Biophysics in the School of Veterinary Medicine and Science, has achieved a transformative feat.

Dr Borkar developed a powerful method that combines a cutting-edge mass spectrometry technology called cryogenic OrbiSIMS – a unique imaging capability of the University, with advanced computational modelling and automation. This combination enabled the team to analyse attomole quantities of RNAs and determine their 3D structures at par with industry standards, in a matter of days.

This innovative approach promises significant advancements in the scope, accuracy, and speed of RNA structural biology and will accelerate the development of RNA-based therapeutics.

1. 7SK is the human RNA implicated in HIV infection, we investigated this as a case study for the paper.
7SK is the human RNA implicated in HIV infection, we investigated this as a case study for the paper. Credit: The University of Nottingham

Dr Borkar said: “RNAs are one of the most difficult molecules to study via structural biology. OrbiSIMS is at least 1000 times more sensitive for studying RNAs compared to other structural techniques typically used in our field.

“With our OrbiSIMS guided pipeline, we can now determine RNA structures in a matter of days,  instead of months. This incredible sensitivity and speed will now help us to study previously intractable targets within narrow drug development timeframes.”

The OrbiSIMS instrument was developed at the National Physical Laboratory, UK in consultation with GSK. Nottingham was the first University in the world to own and operate the OrbiSIMS instrument.

The full study can be found here.

This is where the Nottingham team, led by Dr Aditi Borkar, Assistant Professor in Molecular Biochemistry & Biophysics in the School of Veterinary Medicine and Science, has achieved a transformative feat.

Dr Borkar developed a powerful method that combines a cutting-edge mass spectrometry technology called cryogenic OrbiSIMS – a unique imaging capability of the University, with advanced computational modelling and automation. This combination enabled the team to analyse attomole quantities of RNAs and determine their 3D structures at par with industry standards, in a matter of days.

This innovative approach promises significant advancements in the scope, accuracy, and speed of RNA structural biology and will accelerate the development of RNA-based therapeutics.

Dr Borkar said: “RNAs are one of the most difficult molecules to study via structural biology. OrbiSIMS is at least 1000 times more sensitive for studying RNAs compared to other structural techniques typically used in our field.

“With our OrbiSIMS guided pipeline, we can now determine RNA structures in a matter of days,  instead of months. This incredible sensitivity and speed will now help us to study previously intractable targets within narrow drug development timeframes.”

The OrbiSIMS instrument was developed at the National Physical Laboratory, UK in consultation with GSK. Nottingham was the first University in the world to own and operate the OrbiSIMS instrument.

The full study can be found here.

Journal: Nature Communications
DOI: 10.1017/9781107297227
Method of Research: Experimental study
Subject of Research: Cells
Article Title: Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution
Article Publication Date: 22-May-2024

Media Contact

Charlotte Anscombe
University of Nottingham
charlotte.anscombe@nottingham.ac.uk
Office: 115-7484417

www.nottingham.ac.uk

Media Contact

Charlotte Anscombe
University of Nottingham

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