Genetics and Biochemistry News

Naegleria fowleri, also known as the brain-eating amoeba, thrives in warm freshwater lakes, ponds and rivers. Though infection is rare, if water containing the amoeba is forced up a person’s nose while swimming or diving, the amoeba can travel to the brain. This will cause primary amoebic meningoencephalitis, an almost always fatal infection that results in tissue damage and hemorrhagic necrosis.

Professor Jim Morris is part of a research group at the Clemson University Eukaryotic Pathogens Innovation Center (EPIC) that has identified a compound that inhibits a key enzyme that brain-eating amoebas need to live.

After reading a 2020 scientific paper from the University of Texas MD Anderson Cancer Center, Jillian McKeon, a postdoctoral fellow in the lab, learned of a compound, HEX, that blocked a critical metabolic pathway in certain types of brain cancer cells. HEX blocked enolase, an essential enzyme involved in glycolysis, which is a series of reactions that extract energy from glucose and is necessary for cell growth.

This information eventually led to the discovery that that inhibitors of sugar metabolism designed to treat brain cancer are toxic to N. fowleri by the Morris Lab.

Morris’ lab tested HEX against N. fowleri grown in the lab and found it was more potent against the amoeba than it was the brain tumor. Researchers tested HEX in an animal model by delivering the compound intranasally, they found that it extended the life of infected rats compared to rodents that did not receive the compound, but it did not kill all the amoeba. Morris said he thinks that it didn’t kill all of the amoeba because they couldn’t keep the level of HEX high enough for long enough.

“The experiments weren’t exhaustive. We didn’t try every dose. We didn’t try combinations with other drugs. But what we showed was that when you put the compound up their noses, it meaningfully extended their lives,” Morris said.

The Morris Lab is working with Jessica Larsen, Carol and John Cromer ’63 Family Endowed Associate Professor in Clemson’s Department of Chemical and Biomolecular Engineering and a researcher at EPIC, who focuses on drug delivery, biomaterials and nanotechnology.

Larsen encapsulated the HEX molecule into a nanoparticle made of polymers, called polymersomes, that can help deliver drugs to the brain. Larsen’s group is researching ways to administer the drug.

“The brain-eating amoeba gets into the brain through the nose, so we’re looking to hijack that route for therapy,” she said.

The hope is the brain-eating amoeba research eventually opens a new avenue of easy at-home or out-of-hospital administration for neural therapeutics.

Detailed findings for the research involving the Morris lab were published in the journal PLOS Pathogens in an article titled “Enolase inhibitors as therapeutic leads for Naegleria fowleri infection.”

Read more in the Clemson News article. 

Senior genetics major, minoring in psychology Natalie Shay gained a passion for and knew she wanted to pursue an education in genetics since her first AP biology class in high school. When she visited Clemson while looking at colleges, she knew our genetics program would be where she landed.

“I just loved how complex genetics are. It’s what makes us unique but also alike at the same time. It’s also the explanation for many diseases, so it’s a good field to go in since gene therapies are on the rise.”

Natalie has been involved in labs, the Genetics and Biochemistry (G&B) Club and has had a summer internship at the Greenwood Genetics Center (GGC).

“I was the secretary of the G&B club last year, and I’m the vice president this year. Our club promotes fellowship among students and offers networking opportunities.”

The G&B Club provides members with unparalleled experiences in the field of genetics and biochemistry through faculty guest speakers, field trips and networking with other students pursuing research. As vice president of the G&B Club, Natalie assists with coordinating the club’s annual D.C. trip, where students visit the National Institutes of Health, the US Department of Agriculture and occasionally Astrazeneca, a research-based biopharmaceutical company, to give students windows into their future careers.

In addition to the G&B club, Natalie has been involved in two different labs on campus through her academic career. During her freshman and sophomore year, Natalie was part of the Birtwistle Lab, run by Dr. Marc Birtwistle in the Department of Chemical Engineering, where she experimented on cancer cell diagnostics and therapies. The Birtwistle Lab combines computational and experimental methods to understand how cancer cells make decisions, aiming to use this understanding to better predict drug and drug combination responses.

“During my junior year, I wanted to explore my interests in neurobiology, so I joined the George Lab, run by Dr. Juilia George in in the Department of Biological Sciences. We study how early life environmental changes affect gene expression in zebra finch embryos.”

In the summer of 2024 Natalie was accepted for a summer internship at the Greenwood Genetics Center, a non-profit organization that has provided clinical genetic services, diagnostic laboratory testing, educational programs and resources, and medical genetics research to patients for over 50 years.

At the GGC, Natalie got to shadow many lab techniques such as DNA extraction from human blood, RT-PCR, Western Blotting, Oxford Nanopore DNA sequencing (her favorite) and GGC’s special methylation array test called EpiSign. She also got to see their aquaculture center that houses the zebrafish they use in their research experiments.

“The project that I was a part of is called the Genomic Discovery Project (GDP). In the GDP, clinicians refer patients with suspected genetic disorders to the GGC to investigate further. There are 3 tracks in the GDP: Discovery, Resolution, and Treatment.”

Her experience working in different labs across the state has prepared Natalie to pursue her goal of obtaining an M.S. degree in either neuroscience, genetics or a related field after graduating.

“My overall career goal is to combine my passion for genetics and psychology to create personalized treatments for those with psychiatric disorders using tools like pharmacogenomics.”

Last week, Dr. Jim Morris and Ph.D. student Sabrina Pizarro attended the 4th annual REDDI Lab Symposium, where Sabrina presented a poster on her work characterizing putative T. brucei NHE transporters titled, “Exploration of Putative Sodium/Proton Excahngers in Trypanosoma brucei.”

In addition, Sabrina Pizarro has been awarded an EPIC Graduate Translational Research Assistantship (GTRA). The GTRA is a pilot program in its second year sponsored by the Eukaryotic Pathogen Innovation Center (EPIC), the Graduate School, Clemson University Research Foundation (CURF) and the REDDI Laboratory.

The primary objective of this assistantship is to provide EPIC Ph.D. students with a broad range of translational experiences that will be of importance to them over their careers.

This spring, Sabrina will intern in the REDDI lab to gain experience working in a clinical lab setting. The Research and Education in Disease Diagnosis and Intervention Laboratory (REDDI Lab) is home to Clemson University’s first high-complexity Clinical Laboratory Improvement Amendments (CLIA) certified facility.

In addition to learning RT-PCR based diagnostic panels, she will learn to utilize robotic plate readers allowing for higher throughput of the trypanosome drug discovery assays performed in the Morris lab.