R-loops: from molecular principles to their roles in human disease

Every time a cell reads its DNA to make a protein, it creates a temporary three-stranded structure called an R-loop—a hybrid of DNA and newly made RNA that can either help or harm the cell. These R-loops are essential for normal cell function, but when they build up uncontrollably, they are linked to devastating diseases such as cancer and neurodegeneration. Scientists know R-loops exist, but they do not fully understand what keeps them in check. This project aims to identify the molecular factors that control R-loop behaviour in healthy cells, using advanced techniques to map where R-loops form, how they are removed, and how different regulatory proteins interact. This is fundamental science. There is no immediate clinical application. However, understanding the basic principles of R-loop regulation could eventually reveal why certain cells become vulnerable to damage in diseases like amyotrophic lateral sclerosis (ALS) or certain cancers. In the longer term, the work may point to new therapeutic targets—proteins or pathways that could be manipulated to prevent R-loop accumulation from tipping cells into disease. Past discoveries in fundamental RNA biology have already led to mRNA vaccines and gene-silencing therapies.