Athens, Ga. – Researchers at the University of Georgia have received a $1.8 million grant from the W.M. Keck Foundation to discover the fundamental cellular changes that cause debilitating neurological disorders, including Alzheimer’s disease, autism and intellectual deficiency.
A team of scientists from UGA’s Complex Carbohydrate Research Center will study the role of glycans-structurally diverse sugar molecules that adorn the surface of every cell in the human body-in the development of these diseases, which may open the door to new therapies.
“We know very little about what’s happening on the surface of cells in people with neurological disorders,” said Michael Tiemeyer, professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences and principal investigator for the project. “But what we do know is that glycans control a lot of what happens between cells, and we can use technology developed at the CCRC to examine what role these molecules play in disease mechanisms.”
Once thought to be a relatively unimportant part of the cell, scientists now recognize that complex sugar chains exert control over cell-cell communication and essential cellular behaviors, so even small changes in the structure and behavior of glycans can have profound effects on human health and disease.
“Human diseases disrupt the way sugars are produced and attached to proteins and lipids throughout the body, but it turns out that cells in the brain are particularly sensitive to this kind of change,” said Lance Wells, Georgia Research Alliance investigator, professor of biochemistry and molecular biology and co-investigator for the project. “If we can identify these disruptions, we can begin looking for new and existing drugs that might prevent them.”
Members of the research team have already identified a number of glycan targets that are implicated in Alzheimer’s, autism and intellectual deficiency, which they will study more closely in model organisms like mice and zebrafish and in brain cells derived from reprogrammed human cells.
This approach will help them understand whether changes in glycans are a side effect of the disease or the root cause. They may then test drugs that inhibit these changes to see if the disease symptoms are reversed.
“There are already a number of drugs available on the market that affect the way glycans are produced and how they function, and these compounds could potentially be therapeutic for some of these disorders,” said Richard Steet, associate professor of biochemistry and molecular biology and project co-investigator.
“We have access to hundreds of drugs that have been proven safe, and we can do high-throughput screens to see which drugs affect glycan production,” Wells said.
These studies are a close collaboration between CCRC scientists and co-investigators in the Center for Molecular Medicine and the department of cellular biology at UGA, as well as with basic scientists and clinical geneticists at the Greenwood Genetic Center in Greenwood, South Carolina, and the Clinic for Special Children in Strasburg, Pennsylvania.
“This is an exciting new initiative designed to advance our understanding of the role of glycans in biology,” said David Lee, UGA vice president for research. “There is no better team to do this pioneering work than the experts at the world-class CCRC.”
Ultimately, the researchers expect that their investigation will lead not only to new therapies, but also to a fundamentally new understanding of how diseases develop and how basic cellular processes depend on appropriate glycan production.
“This really is pioneering work,” Tiemeyer said. “We’re not exactly sure what we will discover, but we are taking some of the first important steps, and the potential impact is tremendous.”
Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical, science and engineering research. The Foundation also maintains an undergraduate education program that promotes distinctive learning and research experiences for students in the sciences and in the liberal arts, and a Southern California Grant Program that provides support for the Los Angeles community, with a special emphasis on children and youth from low-income families, special needs populations and safety-net services. For more information, see www.wmkeck.org.