Four chemistry students from the University of St Andrews have helped to discover a class of molecules that can help accelerate DNA repair which could in turn help treat of diseases such as Alzheimer’s.
The undergraduate students – Nicholas D’Arcy-Evans, Kirill Mamonov, Josephine Stewart and Marek Varga – were all co-authors on a paper published in leading journal Science based on cutting-edge medicinal chemistry research carried out at the Karolinska Institutet in Stockholm, Sweden.
The discovery opens new avenues for the treatment of diseases which result from DNA damage, such as Alzheimer’s disease, certain cancers and lung conditions, and the compounds they have identified should slow down the ageing process.
The study improved the function of a protein called OGG1, an enzyme that repairs oxidative DNA damage using a method called organocatalysis. The researchers examined how catalyst molecules bind to OGG1 and affect its function in cells. One of the molecules proved to be of particular interest.
“When we introduce the catalyst into the enzyme, the enzyme becomes ten times more effective at repairing oxidative DNA damage and can perform a new repair function,” says the study’s first author Maurice Michel, assistant professor at the Department of Oncology-Pathology, Karolinska Institutet.
Professor David O’Hagan from the University of St Andrews School of Chemistry said: “I acted as the academic liaison with the students from St Andrews over this period. Despite the pandemic they have conducted impressive and clearly important research and they have been supported by an amazing team of scientists at the Karolinska Institutet. It has been a pleasure to observe what can be achieved even at an early career stage in science when involved in a dynamic team.”
The work was conducted as part of the Industrial Placement year of the students’ MChem degrees and took place over several years in the laboratory of Professor Thomas Helleday.
Three of the students have now graduated, while one – Nicholas D’Arcy-Evans – will resume the final year of their degree in September. Kiril Mamonov graduated in 2021 and is working in Poland, Josephine Stewart will start a PhD in St Andrews in September, and Marek Varga, who worked on placement at the Karolinska when he was a student at Edinburgh University, is now entering the second year of his PhD in St Andrews.
Nicholas said: “To be involved in work like this was far beyond anything I expected during the placement year. It was fantastic to learn from and work alongside leading scientists to answer such a challenging question. We believe that the discovery may shift the way we approach medicinal chemistry – where drugs are designed for enzyme activation, rather than inhibition. I’m excited to see where this goes and how it can help patients in the future.”
Dr Georg Haehner, student placement coordinator, said: “In our placement programme we collaborate with industrial companies and research labs to offer our students the opportunity to work on a scientifically challenging project in an industrial research environment as part of their degree.
“The Helleday Labs in Sweden are among the world leaders in developing novel treatments for cancer using medicinal chemistry. For this reason, we are delighted to engage with their team, where our students gain practical professional experience alongside some of the best researchers in medicinal chemistry, which is reflected by the publication.”
The paper ‘Small molecule activation of OGG1 increases repair of oxidative DNA damage by gaining a new function’ is published in Science and is available online. (DOI: 10.1126/science.abf8980).