Feb 22, 2018

AUSTIN, Texas — The National Science Foundation has awarded Andrea Holgado, a biological sciences associate professor at St. Edward’s University, a four-year, $600,000 grant to study a mutation in roundworms that could shed light on the importance of "cellular recycling" for the proper development of the nervous system. One day, this basic research may contribute to our understanding of the development of neurological diseases such as schizophrenia and bipolar disorder in humans.

Holgado and her research group, including St. Edward’s University undergraduates Nicholas Ashley, Riley Firth, Fiorella Hernandez, Bianca Rosas, Mikaela Wilson, and research technician Hailey Trombley, began the study this spring.

The study hinges on a cellular process called autophagy, which is from the Greek words auto-, meaning “self” and phagein, meaning “to eat.”

“Autophagy is a mechanism in cells that is similar to a recycling center. You can think about the cell as a city, where you have all of this waste, and rather than accumulating the waste, you recycle,” Holgado said. “We think if we can manipulate the recycling system, or somehow enhance the mechanism, we may find a way to modulate genetic problems such as bipolar disorder.”

The goal of the study is to gain a better understanding of a mutation found in C. elegans (roundworms) that results in lower UNC-33 protein levels. Holgado hypothesizes that the lack of protein may affect how well the recycling system works, thus influencing how neurons grow and neural networks develop in the roundworm. 

Holgado was inspired by studies that have found a specific protein, called DPYSL2/UNC-33, needs to be present at very high levels for the development of a healthy human neural network. If the protein level is low, the likelihood of that person developing schizophrenia is increased by two-fold, according to one study that found that changes in DPYSL2 expression are associated with susceptibility to schizophrenia in humans.

“This particular protein (DPYSL2) is important for developing a healthy brain. If you don’t have enough of this protein, you can develop a brain that is very fragile and susceptible to stress,” Holgado said. 

What scientists don’t yet understand is how the protein influences the recycling process in a living organism (in vivo), which is where C. elegans will be useful, Holgado says. Holgado and her research group plan to study a mutant gene in C. elegans that produces no protein in vivo and then analyze the effects that lower protein levels have on the whole organism. 

“We have the molecular tools to study what would happen to a whole organism if you were lacking the protein, expressing less of it or expressing normal levels,” she said. “These are the types of questions we are asking, and I’m training undergraduates to approach these questions using C. elegans and contribute with new findings.”

Once complete, Holgado’s research group hopes that their study will help to explain how protein levels and the cell recycling process reveals itself in the human brain. The long-term goal is to investigate the formation and maintenance of neuronal circuitry in the context of mental health and disease. Preliminary findings from Holgado’s research group will be presented at the 2018 Society for Neuroscience conference in November in San Diego, California.