Dr Magdalena Crossley awarded £2 million Wellcome Development Award

Dr Magdalena Crossley has been awarded a £2 million Wellcome Career Development Award to investigate how unusual RNA-DNA structures contribute to cancer and other diseases.

The highly competitive scheme supports researchers with the potential to become international leaders in their fields, funding ambitious programmes to deliver major advances in understanding human health.

The award will support Dr Crossley’s research into RNA-DNA hybrid structures known as R-loops. RNA is a molecule that carries instructions from DNA to make proteins. While DNA is the long-term storage of genetic information, RNA is the short-term messenger. Sometimes, as it is being made, RNA can reattach to the DNA it came from, forming a structure called an R-loop.

R-loops are a normal part of cell biology, helping to control which genes are switched on or off. However, if R-loops exist for too long or form in the wrong locations, they can lead to breaks in DNA and make the genome unstable. Faulty control of R-loops has been linked to cancer, autoimmune conditions and neurodegeneration, though how it causes disease remains unclear.

Recent work from the Crossley lab uncovered a previously unknown pathway connecting harmful R-loops with DNA damage and activation of the body’s immune response. The research showed that some harmful R-loops are cut out of the genome by enzymes, releasing fragments of RNA-DNA hybrids which then leave the nucleus and build up in the cytoplasm, the main body of the cell. The cell mistakes them for a sign of infection and switches on innate immune signalling, its first line of defence.

Building on this discovery, the Wellcome-funded programme will investigate what causes harmful R-loops to form and be cut out, how the resulting fragments activate immune signalling, and whether those fragments can escape the cell altogether to pass signals to neighbouring cells.

Using biochemical, imaging and genomic technologies developed in her laboratory, Dr Crossley’s team aims to generate new insights into how genome and RNA biology intersect with immunity, with the potential to reveal new therapeutic approaches for cancer and other diseases.

Join the team

To deliver the programme, Dr Crossley is recruiting several new members over the coming months, including a Senior Scientific Associate, Postdoctoral Researcher and Research Assistant. See our vacancies page or contact Dr Crossley directly to discuss opportunities.

 

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