Graduate student Heankel Lyons’ research made the cover of Cell last year for her discovery that floppy regions of proteins rely on a pattern of electrical charges to carry out their work in activating genes.

As she continues her studies to see how this system can be hijacked by cancer, her creative experiments and meticulous efforts have won her the 2024 Nominata Award, the highest honor bestowed on a student of the UT Southwestern Graduate School of Biomedical Sciences.

Ms. Lyons’ interest in research began when a family member developed a rare disease and she learned the condition had no cure. She became fascinated with neuroscience.

Ms. Lyons, a fourth-year student in the Genetics, Development and Disease Ph.D. Program, focused her research on disordered regions of proteins and how their surprisingly specific interactions with one another organize and regulate the activation of gene expression. Unlike textbook models in which proteins fold into particular shapes to carry out their functions, disordered regions flop loosely, leaving researchers mystified as to how such regions play a role in a process that requires such precise control.

“That was my challenge – to understand the mechanism and explain the specificity,” Ms. Lyons said.

Her investigation revealed that the pattern of electrical charges on disordered regions of proteins drives specific and functional interactions regulating gene expression.

“Heankel really sets the standard for rigor and creativity in the lab,” said her mentor, Ben Sabari, Ph.D., Assistant Professor in the Cecil H. and Ida Green Center for Reproductive Biology Sciences and of Molecular Biology and Obstetrics and Gynecology. “She excels at having a big idea and following through.”

As a teenager, Ms. Lyons became interested in research when a family member developed a rare neurodegenerative disease. “I got curious about how this disease could happen, and I was shocked that there was no cure for rare diseases like this,” she said.

She attended Wellesley College in Massachusetts, where she earned her bachelor’s degree in neuroscience, and came to UTSW in 2018 as a Research Assistant.

Ben Sabari, Ph.D., Assistant Professor in the Cecil H. and Ida Green Center for Reproductive Biology Sciences and of Molecular Biology and Obstetrics and Gynecology, mentors Ms. Lyons in his lab. “She excels at having a big idea and following through,” Dr. Sabari said.

“My background was in how neurons interact in networks to produce an output. Then I heard Dr. Sabari talk about proteins in a way I hadn’t heard before,” she said. “Proteins also form networks that expand to create higher-order assemblies, known as condensates, which have properties not found in individual proteins.”

Ms. Lyons used tools to artificially create condensates and found that they selectively concentrate the molecular machinery for activating genes. By careful and clever manipulation of disordered sequences together with a readout of gene activation, she deciphered the molecular connection between sequence and function for a disordered region.

She also showed that the pattern of positive and negative charges in the disordered regions was necessary, and that other disordered regions demonstrate similar patterns. She and her colleagues published this research in Cell in 2023, in a paper that has already been cited about 90 times.

“When you bring these charged disordered regions together in a concentrated environment, they form a network of interactions that selectively concentrates RNA polymerase II and its positive regulators while excluding its negative regulators,” said Dr. Sabari, also a member of the Harold C. Simmons Comprehensive Cancer Center. “Heankel’s investigation has shown that there is a language encoded in disordered regions that imparts specificity. This is having a major impact on our understanding of how protein disorder is used to organize and regulate gene expression.”

Ms. Lyons is now involved in a follow-up study looking at how cancer can hijack disorder-mediated specificity to turn on the wrong genes, added Dr. Sabari. “I am excited about using Heankel’s discoveries to develop therapeutic strategies that target this novel disease mechanism,” he said.

The Nominata was established in 1980 by the Graduate Student Organization to promote academic excellence and research achievement. The winner receives a monetary award and presents their research to the UT Southwestern community. Ms. Lyons’ talk is scheduled at 4 p.m., May 8 in NL3.120.

A Nominata finalist, Yichi “Tony” Zhang, Ph.D., also a student in the Genetics, Development and Disease Graduate Program, received a Dean’s Discretionary Award. Dr. Zhang completed his Ph.D. last summer in the lab of Eric Olson, Ph.D., Chair of Molecular Biology. His research involved identifying the contribution of the myogenin-myostatin axis to cancer cachexia-induced muscle atrophy and establishing the role of the nuclear envelope protein Net39 in muscle development, maintenance, and disease. This work appeared in Nature Structural and Molecular Biology and the Journal of Clinical Investigation.