Researchers are working to advance the field of glycoscience and reveal the important role of carbohydrates in human health and disease. In a narrow sense, glycobiology is the study of the structure, biology, and evolution of sugars, the carbohydrates and sugar-coated molecules found in every living thing. As a recent symposium at MIT showed, the field is in the midst of a renaissance that could reshape scientists' understanding of the building blocks of life.
Glycobiology was originally coined in the 1980s to describe the fusion of traditional studies in carbohydrate chemistry and biochemistry, and now encompasses a broader range of multidisciplinary ideas. In fact, "glycoscience" may be a more appropriate name for this rapidly growing field, as it is widely used not only in biology and chemistry, but also in bioengineering, medicine, materials science, and more.
"It is becoming increasingly clear that these glycans play a very important role in health and disease," said Laura Kiessling, professor of chemistry at Novartis. "It may seem daunting at first, but designing new tools and identifying novel interactions requires exactly the kind of creative problem-solving skills that MIT students possess."
Carbohydrates include a variety of molecules with linear and branched structures that are essential for basic biological functions. From the intricate sugar chains that surround the surface of most cells to the conjugated molecules where sugars attach like scaffolds to lipids and proteins, all cells in nature are coated with these sugar molecules. They are absolutely fundamental to life. For example, Kiesling points out that the most abundant organic molecule on Earth is the carbohydrate cellulose.
"Sperm-egg binding is facilitated by interactions between proteins and carbohydrates," she said. "Without these interactions, none of us would exist."
While talking about carbohydrates and sugar may make some people focus on diet, sugar is actually one of the most important biological macromolecules. They store energy and, in some cases, like cellulose, provide the structural framework for multicellular organisms. They mediate cell-to-cell communication, influence host-parasite interactions, and influence immune responses, disease progression, development, and physiology.
"It turns out that until recently we didn't know that there was such a rich array of structures in the body that serve so many different biological functions," said Katharina Ribbeck, the Andrew and Erna Viterbi Professor of Bioengineering. "With knowledge expanding so rapidly, it feels like we are only beginning to understand the diversity and importance of these functions to biology."
As the prevalence and criticality of these molecules become better understood, researchers in applied fields such as biotechnology and medicine have turned their attention to glycoscience as a tool to identify disease drivers.
Many diseases are linked to defects in the way glycans are made in the body or problems with glycosylation, the process by which carbohydrates attach to proteins and other molecules. This includes some forms of cancer. There are even studies showing that cancer cells wrap themselves in certain glycoproteins to evade the immune response.
On the other hand, sugars may also be a treasure trove of potential treatments. For example, the blood thinner heparin, one of the world's best-selling prescription drugs, is a carbohydrate-based drug.
Sugar-binding proteins such as mangans and lectins even help influence microbial exchange in the body from the brain to the mucus lining of the gut. Sugars hanging from the mucus interact with microorganisms, allowing good microbes to enter and reducing the virulence of problematic microbes, by interfering with cell signaling or preventing pathogens from releasing toxins.
Despite the importance of this "sugar coating", for a long time molecular biologists have only focused on nucleic acids and proteins and paid relatively little attention to the sugars that coat them.
"The tools that we have to study the function of other molecules basically don't exist for glycans," said Kiesling, who is also a member of the Broad Institute of MIT and Harvard.
For example, a cell's DNA and RNA sequences can predict the proteins the cell makes, so scientists can use genetically encoded tags to track a protein's location and role. But the structure of glycans is not so clearly encoded in a cell's DNA, and a protein can be decorated with many different carbohydrate chains.
In addition, carbohydrates come in many forms and break down rapidly in the blood, making it difficult to synthesize glycans or target them for drug development. Therefore, creative new methods are needed to track them.
This is a classic chicken or egg problem. As scientists better understand the importance of glycans to many biological processes, this has led them to develop better tools to study glycans, which in turn has generated more data about the function of these molecules. In fact, the 2022 Nobel Prize was awarded to Carolyn Bertozzi of Stanford University, a pioneer in glycobiology for her work tracking molecules in cells, which she and others applied to glycans.
But artificial intelligence can facilitate an evolutionary leap in the field.
"I think glycobiology is more ripe for AI interpretation than almost any other field," Liebeck said. AI could allow scientists to read the "glycocode" the same way they read the human genome, she explained. This will allow researchers to predict the actual function of a glycan based on data on its structure. From this, it is possible to identify which changes cause disease or increase susceptibility to disease and, most importantly, find ways to repair these deficiencies.
The growing interest in computing reflects the inherently interdisciplinary nature of glycoscience from its inception.
Taking MIT alone as an example, relevant research spans the entire institute. Keesling described MIT as "a paradise for interdisciplinary research," which has led to significant advances in the field in biotechnology, cancer research, brain science, immunology and more.
In the chemistry department, Kiessling is studying carbohydrate-binding proteins and how their interactions with glycans affect the immune system. She is also working with Bryan Bryson, associate professor in the Department of Bioengineering, and Deborah Hung, a core faculty member at the Broad Institute of MIT and Harvard, to use carbohydrate analogs to test differences in the South African TB strains. Meanwhile, Jessica Stark, assistant professor in the Department of Bioengineering, is pioneering ways to better understand the role of sugars in the immune system. Tobi Oni, a researcher at the Whitehead Institute for Biomedical Research, is studying how to use glycans to help detect and target tumors in pancreatic cancer. Barbara Imperiali, a 1922 professor in the Department of Biology and Chemistry, is studying carbohydrates that coat microbial cells such as bacteria, and Professor Matthew Shoulders in the Department of Chemistry is studying the role of glycans in the synthesis and folding of proteins.
"We are in a very exciting and unique position, combining disciplines to address and answer entirely new questions related to disease and health," Liebeck said. "The field itself is not new, but what is new is that MIT, and MIT in particular, can contribute through a creative combination of science, engineering and computing."
Compiled source: ScitechDaily