Serendipity leads UGA researcher into uncharted territory and a new NIH grant

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Serendipity leads UGA researcher into uncharted territory and a new NIH grant

Ronald Drew Etheridge

Ronald Drew Etheridge, UGA assistant professor of cellular biology, was awarded a five-year grant from the National Institutes of Health to continue his gene-editing work on Trypanosoma cruzi, the parasite that causes Chagas’ disease. (Photo by Donna Huber)

Ronald Drew Etheridge’s scientific career can be characterized by one word—serendipity.

After completing his bachelor’s degree in biochemistry and molecular biology with a Spanish language minor at the University of Georgia, Etheridge set out for Spain, where he traveled and worked as an English teacher. On his return home, and in need of a job, a former coworker mentioned a potential opening for a technician at UGA in the lab of Rick Tarleton, a leader in studying Trypanosoma cruzi, the protozoan that causes Chagas’ disease. While having worked in many labs as an undergraduate conducting basic scientific research, he had never really considered pursuing a study of immunology or parasitology. As luck would have it, his time in the Tarleton lab would spark his scientific curiosity like never before.

“It was the first time science was truly fun for me,” said Etheridge. “I really enjoyed the interesting scientific debates and rigorous research environment fostered in Rick’s lab.”

Realizing he needed further training to be a competent parasitologist, he went on to pursue a Ph.D. at the University of California, Irvine, and postdoctoral training at Washington University School of Medicine. In 2016, Etheridge returned to his alma mater and joined the faculty in Franklin College of Arts and Science’s Department of Cellular Biology and the Center for Tropical and Emerging Global Disease as an assistant professor.

By the time he returned to UGA, his focus had shifted slightly from immunology to molecular parasitology as he delved into host-pathogen interactions involving the protozoan parasite Toxoplasma gondii. But serendipity struck again. Upon his return to UGA he realized that Tarleton and colleague Roberto Docampo had pioneered the use of the gene-editing system CRISPR-Cas9 in Trypanosoma cruzi. Their research opened up the possibility of studying this highly neglected parasite at the molecular level for the first time. This work ultimately led Etheridge to pilot gene-editing projects in T. cruzi with a focus on explaining how this parasite directly interacts with and manipulates its host.

“One of the great things about academic research is the ability to be flexible and go down new avenues of research when they present themselves,” said Etheridge.

As part of these pilot studies, Etheridge’s group identified the first protein components of what can be considered the digestive tract of this single-cell parasite. This unique feeding structure starts as a pore on the parasite surface (the cytostome) and is followed by a tubular structure called the cytopharynx that ultimately ends with captured food being sent for digestion in endocytosed vesicles. The Etheridge lab refers to this endocytic feeding organelle as the cytostome/cytopharynx complex, or SPC for short.

“That’s what is cool about science—by chance you find novel things,” said Etheridge.

When this project began, very little was known about how T. cruzi fed on its host to obtain nutrients. Since this initial discovery, the Etheridge lab has identified dozens of SPC-targeted proteins and has uncovered the protein machinery parasites use to catch and bring in food they want to digest.

“Virtually nothing was known about how this structure actually worked,” said Etheridge. “There have been some electron microscopy studies that described the structure, but that’s all we had when we first started. It has been really exciting to work on something so fundamental yet so poorly understood.”

The National Institutes of Health awarded Etheridge a new five-year grant to continue down this path in hopes of deciphering how the SPC works and the role this structure plays in T. cruzi’s parasitic life cycle. The answers to these questions could have wide implications.

“Not only can it help us to devise potential drug treatments for Chagas’ disease, an often debilitating and sometimes fatal disease which adversely affects 10 million people in the Americas,” said Etheridge. “But more broadly, it can also tell us something fundamental about the basic biology of many species of protozoa that also use the SPC structure to capture and digest food.”

 

This story originally appeared at UGA Research News.