University of Georgia

Mapping the structures of sugars

University of Georgia researcher Parastoo Azadi in laboratory
(Photo by Amy Ware)

For three decades, Parastoo Azadi has been elucidating the structure of glycans: groups of complex sugars that cover every living cell. Understanding their structure—and their function—could lead to breakthroughs in a number of fields, from medicine to renewable energy and sustainable materials.

Right now, Azadi has COVID-19 in her sights.

“In order to know the biology, be it of a cancer cell or in this case a virus, you need to know the structure first,” said Azadi, technical director of Analytical Services and Training at UGA’s Complex Carbohydrate Research Center. “Otherwise you don’t know what you’re dealing with.”

Azadi and her CCRC team recently published work detailing the full structure of glycans on the surface of the SARS-CoV-2 spike protein. Many COVID-19 vaccines in development target the spike protein because its surface glycans determine how the virus attaches to human cells.  The spike protein is made up of two subunits, and the glycans on the subunits look different whether they are together or separated, which could make a difference in vaccine development.

“We thought that vaccine companies may only need to use the single subunit that contains the binding region to the human cells,” said Azadi, “so we decided not to look at the whole spike protein together, but instead to study the individual components.”

Her team determined exactly which glycans cover the protein and what their positions are, which can help researchers understand how the virus infects cells.

But Azadi’s own research is only one small part of CCRC Analytical Services & Training’s work. As one of UGA’s core research facilities, AST represents a unique resource for UGA and provides research, service and training in the characterization of carbohydrate structures to universities, government agencies and industry around the world.

She was recently awarded a National Institutes of Health grant that will help support their service and training efforts in the biomedical area in future years.

“Scientists come to us because they have a problem they cannot solve themselves,” said Azadi. “So we have to put different hats on and figure out, with the unique expertise and the sophisticated instrumentations that we have, how best to help solve their problem.”

But it’s not about just having the right tools for the job.

“Most of the time they require us to be creative: We have to develop new techniques, methods or protocols specific to that project,” she said. “We have 30 years of experience doing this, but every time there are new and challenging problems that we have to address.”

Her team, which includes Assistant Director Christian Heiss and a group of researchers with specialized expertise, thrives in the interdisciplinary environment of the CCRC.

At any given time, AST manages about 80 projects and has become the “go to” place for many companies looking to launch a carbohydrate product. Azadi works with industry leaders and government agencies to build a framework around acceptable data packages to ensure that any carbohydrate therapeutics, vaccines, food, drinks or cosmetics on the market are safe and contain exactly what they are supposed to contain.

3d illustration of SARS-COV2 spike glycoprotein and its human receptor ACE2
SARS-COV2 spike glycoprotein and its human receptor ACE2 with glycan positions on both glycoproteins highlighted (Illustration by Daniel S. Rouhani)

Her team’s expertise is also going to play a key role in a new $23 million joint project, with Virginia Tech and other universities, funded by the National Science Foundation. The goal is to build a facility specialized in creating glycopolymers (chains of carbohydrates) with specific applications, such as a new plastic or drug. Azadi’s team will make sure the polymers have the exact structure—and, therefore, function—that they need.

“The polymers we have in nature have complicated structures we cannot change,” said Azadi. “We want to be able to create the exact structures that we want. So we’re synthesizing on demand, but it’s much harder with glycans because of their complexity, and it’s difficult to position each unit exactly where you want them.”

Azadi, together with CCRC Director Alan Darvill, also heads the Department of Energy Center for Plant and Microbial Complex Carbohydrates. The center is the longest-funded multi-PI center at the CCRC, with research focused on the structure, function and biosynthesis of complex plant and microbial cell wall carbohydrates that have many potential applications for commercial use.

To share the knowledge built working at the cutting edge of glycoscience, Azadi coordinates specialized training courses in carbohydrate analysis annually for about 50 people. COVID-19 drove the course online this year, and in August she and CCRC faculty trained more than 300 scientists from all over the world.

“COVID has presented us with so many challenges, but also some opportunities,” said Azadi. “We were able through the training courses to interact with a large number of scientists who would never have had the chance to participate in person, really wonderful scientists who just don’t have the capability to travel.”

In September, Azadi was also asked by the National Institutes of Health and U.S. Food & Drug Administration to organize a training course in new glycoscience techniques for 40 of their scientists. She enjoys sharing her excitement over the doors that carbohydrate science could open.

“The first six months of my Ph.D. really opened my eyes to this hidden gem [of glycoscience], like a black box that needed to be opened,” said Azadi, who earned a Ph.D. in biochemistry in 1991 at Imperial College London. “The field was really young at the time and very few people were working in this area, especially structural aspects of it.”

After her Ph.D., she continued to gain key expertise in mass spectrometry, working for a company called M-Scan in the U.K. and providing analytical services to the pharmaceutical industry, before joining CCRC in 1994. Since 2001 she has been technical director of AST.

“I hope students coming into this field will still feel the excitement that I felt 30 years ago,” Azadi said. “There’s just still so much potential.”