Researchers from the Francis Crick Institute are part of an international team that has received a new award from the Royal Society of Chemistry for the development of new chemical tools that can identify how cell surface sugars change during diseases such as cancer.
The ‘GlycoTrackers’ team, made up of researchers including from the Crick, Imperial College London and Stanford University, have received the Society’s new Chemistry Biology Interface Division Horizon Prize, the Rita and John Cornforth Award.
The Society’s Horizon prizes celebrate teams or collaborations that are opening up new directions and possibilities in chemical science, through ground-breaking scientific developments.
As part of their work, the team studied glycans, sugar molecules that cover every cell in the human body and which are involved in processes essential for life. These molecules come in different shapes and sizes, and small changes can have a profound impact on metabolism or the ability to respond to disease.
Unlike other biomolecules, glycans are not directly encoded by DNA. Instead, they are built from simple sugar building blocks by glycosyltransferases enzymes. When these enzymes do not work properly, this can cause changes in the glycans they produce, for example, making them more or less active and some of these glycan changes are commonly seen in cancers.
Their make-up also means glycans are more challenging to study than other biomolecules and so their role in health and disease is not fully understood.
Over the course of two-decades, the GlycoTrackers team developed a set of chemical “Precision Tools” that allow the direct mapping of glycans by taking a detailed look at the activity of glycosyltransferases. The team successfully mapped the products of, and were able to detect abnormalities in, individual glycosyltransferases. This included being able to identify which glycans are modified by which glycosyltransferases within a cell.
This technology could give scientists the capacity to build a more detailed view of basic cell functions, and characterise changes in cell surface glycans during the formation of diseases such as cancer, helping guide development of the next generation of diagnostics and therapeutics.
Ben Schumann, group leader at the Crick and lecturer at Imperial College London, says: “The whole field of glycobiology – despite 100 years or more of work – is still shrouded in mystery, because there are so many experimental obstacles to unravelling the roles of glycans. By combining chemistry and biology, we hope that our Precision Tools will provide a way to complement existing approaches in the biosciences.
“This prize lists scientists from five different countries - it's never just one person who makes something work, you need experts in pretty much every face of chemical biology.”
Omur Tastan, former senior laboratory research scientist at the Crick says: “Traditionally, studies on glycans have been slightly incomplete and we haven’t had the whole story when it comes to the complex world of glycoproteins.
“Now we have a toolbox to ask the right questions on the activities of glycosyltransferases and test our hypotheses completely.”