Researchers develop platform to advance research on carbohydrates

Researchers at the Massachusetts Institute of Technology (MIT) have devised a tool that can assist with identifying carbohydrate-binding proteins, a new MIT press release said. 

Researchers working in the field of carbohydrates face a significant challenge due to the limited tools available to understand the role of sugars. In an effort to overcome this obstacle, a team of scientists led by Professor Barbara Imperiali has developed a groundbreaking platform that addresses the limitations of current methods, says their study, published in a recent issue of ACS Chemical Biology. It offers a new approach to identifying carbohydrate-binding proteins with diverse and programmable specificity. 

Carbohydrates are molecules that play vital roles in various biological processes. However, their intricate structures have traditionally made them difficult to study, the press release said.

Researchers have typically used lectins, sugar-binding proteins derived from plants or fungi, to see how carbohydrates respond. The lectin proteins, however, come with drawbacks in terms of their large size, weak binding ability, and limited sugar-detection capabilities. 

That challenge prompted the researchers to find alternative ways to decipher the complexities of carbohydrates. Imperiali's team employed directed evolution and innovative screening techniques to identify carbohydrate-binding proteins from proteins that traditionally lacked binding ability, the release said. This breakthrough lays the foundation for the discovery of smaller binding proteins, offering the potential to piece together carbohydrate structures and detect specific sugars within them.

Researchers will be able to springboard off this to develop the freedom to pursue sugar targets of their choosing, unrestricted by the limitations of lectins or the challenges associated with generating antibodies, MIT said. This breakthrough also opens doors for collaborations with engineering communities to enhance the efficiency of glycobiology's yeast surface display pipeline, which currently works well for proteins but requires modification to accommodate the complexity of sugars, the news release said.

Future applications of this innovation range from diagnostics to therapeutics, and the breakthrough has the potential to revolutionize cell imaging, the scientists say.

By modifying binders with fluorophores, researchers can easily visualize tissues and cells. "For example, chemistry Professor Laura Kiessling's research group works with Mycobacterium tuberculosis (Mtb), which has an unusual cell wall composition with unique, distinct, and exclusive sugars. Using this method, a binder could potentially be evolved to that particular feature on Mtb," the release said. This approach could shed light on disruptions in a patient's microbiome, the MIT article said.

Additionally, it could facilitate the screening of oral or gastrointestinal microbiomes, highlighting imbalances therein. In the future, binders may even have therapeutic applications, such as selectively clearing specific bacteria from the gastrointestinal tract or mouth based on their sugar displays, it continued.

The researchers' platform represents a significant step forward in carbohydrate research, offering a new avenue to explore the complexities of these molecules, and has paved the way for advancements in diagnostics, therapeutics, and cell imaging, providing researchers with the tools they desperately need to unlock the mysteries of carbohydrates, the release says.