Genes affecting worm behavior found to be relevant to neurological disease in humans

As an undergraduate student in The University of Texas at Arlington's Honors College, Hannah Selvarathinam knew she wanted to conduct research. Near the end of her first year at UTA, the Keller native reached out to the lab of biology Assistant Professor Piya Ghose.

"Hannah has been a very impressive scholar from Day 1," Ghose said. "She had the foresight to reach out for research opportunities very early on."

Ghose brought Selvarathinam in to work on one of the lab's core projects related to the genetics of cell death, modeled in the roundworm Caenorhabditis elegans. Selvarathinam's work eventually led to her honors thesis, focused on brain health and behavior. The result is a new peer-reviewed publication detailing the genes affecting worm behavior that also are relevant to neurological disease in humans.

Through combing the literature and discussing her findings with me, she was able to make connections between the genes she was already studying as part of her cell biology project with her undergraduate psychology major and interests in human health. Hannah drove this project and regularly communicated with me for guidance and to share her exciting results. She took on the brave task of adapting and optimizing a published behavioral protocol for her project, which is exceptional for such a young trainee."

Piya Ghose, Assistant Professor, The University of Texas at Arlington

For her study, Selvarathinam leveraged the fact that worms have similarities in their genes to humans and predictable behaviors that are easy to study. She proceeded to optimize an experi-mental protocol that aimed to link the mental illness schizophrenia to neurodegenerative disease using worm behavior.

"Normally, worms spend much of their time eating. But if they are interrupted by physical insult, they briefly stop in a manner similar to the startle response in humans," Selvarathinam said.

Schizophrenia has similar symptoms, and one hallmark is abnormal reactivity to a continued stimulus. Essentially, individuals with the illness take longer to become accustomed to a stimulus than those without.

"What we found in our study is that healthy worms, as expected, momentarily stopped eating when they were exposed to a stimulus, but soon continued to eat again," Selvarathinam explained. "But for worms with mutations in many of the neurodegeneration genes, such as with those related to hereditary spastic paraplegia and Alzheimer's disease, they continued to eat even after being exposed to the stimulus, which shows a heightened startle response.

"Our publication adds another building block to our understanding of brain disease in the hopes of finding a cure and also highlights C.elegans as a powerful model organism to pursue this goal."

After completing her honors thesis and graduating in winter 2022, Selvarathinam began working as a technician in Ghose's lab while preparing applications for medical school. She's now on track with another peer-reviewed publication for work she has done assisting on one of the lab's cell death projects.

"My research experience complements my goal to practice medicine by teaching me many transferable skills, such as reading scientific literature and applying my knowledge to solve problems and answer interesting questions," Selvarathinam said. "I am grateful for the opportunities I have had at UTA and for the chance to work with the Ghose Lab team. I am also thankful to the Honors College for its wonderful capstone project program. I encourage students to reach out to professors and seek out research opportunities here at UTA."