Exploring Science's Sweet Spot

Joe Caspermeyer, Media Relations Manager & Science Editor
(480) 727-0369 | joseph.caspermeyer@asu.edu

Biodesign Institute Hosts Leaders for Glycobiology Symposium

The Biodesign Institute's Center for Glycosciences and Technology, directed by Lokesh Joshi (second row from bottom, far right), hosted the “Interdisciplinary Translational Glycobiology Symposium.”

Recently, the Biodesign Institute at ASU hosted a two-day gathering of international experts focused on a burgeoning branch of science that attempts to understand how sugars in the body -called glycans- contribute to human health and life.

“Until recently, DNA and proteins were thought to contain all of the information necessary to define the complexity of life,” said Lokesh Joshi, director of the Institute's Center for Glycosciences and Technology and an associate professor of bioengineering. “There is now a paradigm shift occurring where carbohydrate complexity is accepted as the third language of biology and chemistry, and scientists now want to understand this sugar code of life.”

Joshi explains that glycobiology is a complex field with a relatively small number of experts, and this served as his impetus in hosting the “Interdisciplinary Translational Glycobiology Symposium.” The event brought 16 leading research groups from around the world together discuss new innovations, discoveries and future directions in the emergent field.

To understand the complexity of what is sometimes called “sweet biology,” consider that every cell in the body is covered with a dense layer of carbohydrates. These sugars help cells maintain their shape and identity, communicate and attach to each other, and respond to physiological alterations. In addition, up to 70 percent of all proteins made in the human body are decorated with sugars. These decorations are not just ornamental, but have vital functions in the brain, vascular system and immune system. The smallest changes in these structures can have profound implications for diseases including cancer, infectious disease and immune disorders.

Glycobiology also plays a key role in clinical intervention and drug discovery and development and an estimated annual $16 billion therapeutic protein drug market.

In order to make rapid strides in glycobiology, scientists from diverse disciplines have joined forces. For example, in Joshi?s center, immunologists often work side by side with cell biologists, protein engineers, bioengineers and plant scientists during their research endeavors.

“Glycosciences is the poster child for interdisciplinary science,” said professor Robert Woods of the Complex Carbohydrate Research Center at University of Georgia.

In addition to Woods, whose research focus studies the 3-D shapes of glycoprotein structures, other glycoscience leaders present at the symposium were Ajit Varki, Roland Schauer, Hudson Freeze, Hans-Joachim Gabius and James Paulson (full list of participants). Professor Paulson of the Scripps Institute leads the Consortium for Functional Glycomics, a large research initiative funded by the National Institute for General Medical Sciences (NIGMS) to understand the role of carbohydrate-protein interactions at the cell surface in cell-cell communication.

The variety of research talks included presentations and discussions on the role sugars play in invasive bacterial infections, food borne pathogens, protective immune system barriers, tumor growth, evolutionary glycobiology, sugar scaffolds for tissue engineering and congenital disorders of glycosylation (CDG), or genetic disorders which affect human life. Others focused on novel tools to decipher the glyco-code, such as 3-D structural analysis, high-throughput microarray methods and advanced mass spectrometric methods.

Unlike DNA, which is shaped like a string, sugars can form a myriad of tree branch structures to give proteins and lipids (fats) their different forms and functions. For example, for almost every glycan structure, there are unique recognition counterparts called lectins. These proteins physically attach to glycans, binding to the outside of cells to cause changes within the cell or allow cells to clump together. Many infectious agents exploit these targets to invade the human body.

Often, scientists have been stymied by these sticky structures. State of the art analytical tools such as nuclear magnetic resonance (NMR), liquid chromatography (LC), and mass spectrometry (MS) have significantly advanced the knowledge of glyco-structural information, but these are often highly specialized, labor-intensive and time-consuming techniques.

“Glycobiology has suffered from the lack of simpler (but sophisticated) tools. If we are to understand the roles and the complexity of glycan-lectin interactions and the glycome, we need to develop technologies that are amenable to miniaturization and rapid detection of glycans and lectins. We also need novel technologies for glycosequencing,” said Joshi.

To begin to address the problem, Joshi, along with fellow Biodesign researcher and chemical engineering and chemistry professor Joseph Wang, have embarked on a new multi-center effort to advance the detection of these structures by creating nano-scale glycosensors.

The collaboration will allow Wang, who is at the forefront of sensor technology as director of the institute?s Center for Biosensors and Bioelectronics, to design systems that within seconds, could reliably detect different carbohydrate profiles.

“The key will be to identify sugar signatures that are affected by different physiological states,” said Joshi. “If we can multiplex this technology, we could identify up to 100 different structures in an hour.”

Future applications include disease detection and environmental monitoring. Joshi and Wang envision such a device to be about the size of a quarter, that can be used in laboratory or point-of-care settings.

Glycosciences is a new frontier in science and technology. The Biodesign Institute intends to help make fundamental discoveries and also develop novel technologies to make this, so far a field for specialists, more accessible to other researchers ? and bring the discoveries to society. The spirit of the symposium hosted by the Center for Glycosciences and Technology was to discuss the roles of glycans in diseases and connect technologies with biomedical applications.

“For our center, which is less than a year old, the feedback and guidance is integral in helping us to shape the future directions of glycosciences at Biodesign,” said Joshi. “We hope to continue on our success in order to develop novel therapeutics, metabolic engineering and the understanding of genetic and biochemical characterization of carbohydrates.”

It was evident in the two days of discussions that carbohydrates play crucial roles in all organisms from bacteria to humans. However, much work needs to be done to realize the full potential of these sweet molecules of life.