Automated tool enables rapid, large-scale profiling of disease-linked RNA modifications

Researchers have developed a powerful tool capable of scanning thousands of organic samples to detect the transfer of modifications to ribonucleic acid (ARNT) – chemical modifications of the dull RNA molecules which help control how cells develop, adapt to stress and respond to diseases such as cancer and antibiotic -resistant infections. This tool opens up new possibilities for science, health care and industry, accelerating research on disease and allowing more precise diagnoses, to guide the development of more effective medical treatments for diseases such as cancer and antibiotic resistant infections.

Research was led by Smart AMR, in collaboration with Nanyang Technological University (NTU Singapore), University of Florida, University of Albany, Lodz University of Technology and MIT.

Approach the current limits of RNA modification profiling

Cancer and infectious diseases are complicated health problems in which cells are forced to function abnormally by mutations in their genetic material or by instructions from an invasive microorganism. The intelligence research team is among the world leaders to understand how the epitranscriptoma – more than 170 different chemical modifications of all RNA forms – controls the growth of normal cells and how cells react to stressful changes in the environment, such as the loss of nutrients or exposure to toxic chemicals. Researchers also study how this system is corrupt in cancer or exploited by viruses, bacteria and parasites in infectious diseases.

The current molecular methods used to study the vast epitranscriptoma and all the thousands of different types of modified RNA are often slow, with high intensity of labor, expensive and involve dangerous chemicals that limit capacity and research speed.

To solve this problem, the intelligent team has developed a new tool that allows rapid automated profiling of ARNT changes – molecular changes that regulate how cells survive, adapt to stress and respond to the disease. This capacity allows scientists to map cell regulation networks, discover new enzymes and link molecular models to the mechanisms of the disease, opening the way to a better discovery and development of drugs, and diagnostics of more precise disease.

Unlock the complexity of RNA modifications

Smart research, recently published in Nucleic acid searchEntitled “The profiling of the modification of the ARNT reveals the regulatory networks of the epitranscriptom in pseudomonas aeruginosa”, shows that the tool has already enabled the discovery of modifying enzymes of RNA previously unknown RNA and the cartography of the regulatory networks of complex genes. These networks are crucial for cell adaptation to stress and disease, providing important information on how RNA changes control the bacterial survival mechanisms.

Using robotic fluid managers, researchers extracted the arnt from more than 5,700 genetically modified strains of pseudomonas aeruginosa, a bacteria that causes infections such as pneumonia, urinary tract infections, blood circulation infections and wound infections. The samples have been enzymatically digested and analyzed by liquid-tandem-spectrometry chromatography in tandem (LC-MS / MS), a technique that separates molecules as a function of their physical properties and identifies them with high precision and sensitivity.

As part of the study, the process generated more than 200,000 data points in a high resolution approach that revealed new ARNT modifying enzymes and simplified genes controlling how cells react and adapt to stress. For example, the data has revealed that methylthiotransferase Miab, one of the enzymes responsible for the modification of the MS2I6A, proved to be sensitive to the availability of iron and sulfur and metabolic changes when oxygen is low. Discoveries like this highlight the way in which cells react to environmental stress and could lead to the future development of therapies or diagnostics.

The Automated Smart system was specially designed to profile the changes to the ARNT in thousands of samples quickly and safely. Unlike traditional methods – which are expensive, with a high intensity of labor and use toxic solvents such as phenol and chloroform – this tool integrates robotics to automate the preparation and analysis of samples, eliminating the need for dangerous chemical manipulation and cost reduction. This progression increases safety, flow and affordability, allowing large -scale routine use in clinical research and laboratories.

A faster and automated way to study RNA

As a first system capable of quantitative profiling on the scale of the system of arnt modifications on this scale, the tool offers a unique and complete view of the epitranscriptom – the complete set of RNA chemical modifications in cells. This capacity allows researchers to validate the hypotheses on RNA changes, to discover a new biology and to identify promising molecular targets to develop new therapies.

“This pioneering tool marks a transformative advance in the decoding of the complex language of RNA modifications which regulate cellular responses. Put the expertise of the AMR in mass spectrometry and the epitranscriptomic RNA, our research discover new methods to detect the networks of critical complex genes to understand and treat cancer as well as for antibiotic infections.

“By allowing a rapid and large-scale analysis, the tool accelerates both the fundamental scientific discovery and the development of diagnostics and targeted therapies that will fall under urgent global health challenges,” said Professor Peter Dedon, principal co-léger (PI) investigator (PI) at Smart AMR, Biological Engineering Professor and the corresponding author of the document.

Acceleration of research, industry and health applications

This versatile tool has wide applications in scientific research, industry and health care. It allows large -scale studies on gene regulation, RNA biology and cellular responses to environmental and therapeutic challenges. The pharmaceutical and biotechnological industry can exploit it for the discovery of drugs and the screening of biomarkers, effectively evaluating how potential drugs affect RNA and cell behavior changes. This helps the development of targeted therapies and personalized medical treatments.

“This is the first tool that can quickly and quantitatively install RNA modifications in thousands of samples. It has not only allowed us to discover new enzymes and genes of genes modifying RNA, but also opens the door to the identification of biomarkers and therapeutic objectives for diseases such as cancer and antibiotic analysis. AMR and first author of the newspaper.

In the future: advance clinical and pharmaceutical applications

In the future, Smart AMR plans to extend the capacities of the tool to analyze RNA modifications in human cells and tissues, going beyond microbial models to deepen the understanding of the mechanisms of the disease in humans.

Future efforts will focus on the integration of the platform into clinical research to speed up the discovery of biomarkers and therapeutic targets. Translation of technology in an epitranscriptoma -scale analysis tool that can be used in pharmaceutical and health care environments, will stimulate the development of more efficient and personalized treatments.