Sugars in the Spotlight

I’ve always been a little unconventional – perhaps that is what attracted me to glycobiology. There is no template for sugars; they don’t conform to the central dogma of biology – DNA to RNA to protein – but instead are made on an ad hoc basis with a high degree of variability. Of course, that doesn’t mean that glycans are produced at random, but they are controlled by forces that, until recently, we did not fully understand. Scientists working in gene and protein biology can easily amplify and sequence their samples, whereas analyzing glycans is no easy task.

Uniqueness is a common theme when glycobiologists talk about their subject. “Sugars are different, sugars are interesting, sugars are challenging,” is our refrain. It sounds rather evangelical but sugars really are special, and glycobiology attracts a special breed of scientist. While fellow undergraduate students groaned at carbohydrate chemistry lectures, we listened rapt. While conventional biochemists examined gene expression in minute detail, we were struggling to narrow down our analyses to a single tissue. Traditionally, we have been the poor relation to proteins when it comes to funding and tools, and if it wasn’t for our passion for the subject, most of us would have given up years ago. What drives us is the absolute conviction that sugars lie at the heart of some of the most pressing problems facing medical science today, from cancer to malaria to drug resistance.

That conviction is spreading in the wider scientific community; glycobiology is going mainstream. New tools and equipment are allowing sophisticated glycan analyses, which confirm the importance of sugars in all manner of physiological and pathogenic processes. For example, we always knew that glycans played a key role in development – if you alter certain glycosaminoglycans in mouse embryos, their development is so disordered that they die in utero. Now, novel analytical tools allow us to determine the type and amount of different glycans in different tissues throughout development, and pick up a huge amount of beautiful detail that you couldn’t see before, including clues to disease mechanisms and developmental abnormalities.

Life scientists used to working within the rigid confines of genes and proteins are finding themselves thrust into the very different world of glycans – and it scares many of them. I often review grants from people with strong specialties; for example, cancer biology. Imagine they have spent their career studying cancer metastasis, and suddenly find out that a crucial metastasizing factor is a sugar. If they have only ever taken a few classes of carbohydrate chemistry at undergraduate level, they are faced with a pretty big gap in knowledge and skills. Often, they turn to inter-disciplinary collaborations – many of our best collaborations have come when talented scientists in other areas have approached us with this type of problem. It is great to see scientists in other areas taking an interest in glycobiology – and raising the profile of our field – but if glycans are ever to be as well understood as proteins, in the long term we need more dedicated glycobiologists. Glycobiology needs to be taught at undergraduate and PhD level, so that all biochemists have at least a basic grounding. As analysis gets more accurate and glycans give up more of their secrets, I hope more people will choose to join this emerging field. In particular, glycobiology has always been a field that attracts female researchers – my own lab is overwhelmingly female. The strong women who carved out a niche and made great breakthroughs in the field, in the face of scientific, funding and professional barriers, are a continuing inspiration to me, and I hope to see that tradition of female-led research continue.