UGA biochemists create new tool to study biological process in parasites
Researchers in the University of Georgia’s West Laboratory are interested in how unicellular parasites thrive in their environments. Focusing on post-translational modifications of proteins, particularly a crucial process called glycosylation, researchers are gaining insights into how this basic life process in parasites can lead to better treatments for diseases.
Led by Distinguished Research Professor Christopher West, the team focuses on Toxoplasma gondii, a parasite that causes a chronic infection known as toxoplasmosis, and Dictyostelium discoideum, a soil-dwelling social amoeba commonly known as a cellular slime mold. Dictyostelium is an unrelated non-pathogenic model organism with a relatively simple life cycle, making it ideal for laboratory research.
Their colleagues at Boston University, Giulia Bandini and John Samuelson, discovered that dozens of nuclear and cytoplasmic proteins in Toxoplasma are unusually modified by a single sugar called fucose. There were potential parallels with a similar modification of host cell proteins with the key difference being the sugar involved-called GlcNAc, which is important for mediating host cell stress responses.
“This unprecedented finding raised new questions after we found that a similar process occurred in Dictyostelium,” said West, Distinguished Research Professor in Franklin College of Arts and Science’s Department of Biochemistry and Molecular Biology.
When the West lab identified the gene responsible for attaching O-fucose, the door was opened to study its function when it was knocked out in Toxoplasma and Dictyostelium.
“Though the cells still lived, both grew more slowly,” said West, a member of the Center for Tropical and Emerging Global Diseases. “The evidence indicated that several important proteins were less abundant, which consequently compromised their activity in cells.”
O-fucose is difficult to detect through traditional methods, which impedes learning more about its roles. To address this need, Megna Tiwari, a recently graduated biochemistry Ph.D. student in the West Lab, got together with Ron Orlando at the Complex Carbohydrate Research Center and GlycoScientific LLC to generate antibodies that only bind O-fucose on proteins. Her recent study published in mSphere illustrates the power of these antibodies to find and isolate O-fucose in the cell.
“Remarkably, dozens of new proteins were found to bear O-fucose and the images indicate that majority of them appear to be enriched at the nuclear periphery, inviting new ideas for O-fucose at this location,” West said.
This story was originally published at UGA Research https://research.uga.edu/news/uga-biochemists-create-new-tool-to-study-biological-process-in-parasites/