Local biologists looked to the tiny brains of fruit flies and millimeter-long worms for clues about the role genetics play in human neurological disorders.
A study by researchers at Colorado College and the University of Colorado at Colorado Springs, published in the journal Developmental Biology this month, zeroes in on one gene — out of thousands in each of the two organisms — and how it influences the shape of neurons, cells that transmit information within the brain.
Fruit flies and the worms, called C. elegans, were ideal subjects — not only for ethical reasons, but also because the scientists have developed an “unparalleled ability” to manipulate their DNA after decades of studying them, said study author and UCCS associate professor Eugenia Olesnicky.
But the findings are also thought to be applicable in the human brain, where oddly shaped neurons are often found in people with disorders such as autism and schizophrenia.
The study found that the specific gene, known as “SUP-26” in the worms and “Shep” in the flies, affects the shape of a neuron by controlling the translation of messenger RNAs, said Darrell Killian, an associate professor of molecular biology at Colorado College. Messenger RNAs are molecules that convey genetic information from a cell’s DNA to build protein.
“The simplistic view that folks learn — like in intro bio class in high school or even in college at the lower level — is that these messages encode for protein. And once the message is made, the protein is made,” said Killian, who worked on the research. “The reality is, it’s much more complex than that, and the process of when and where and how much a message is translated into protein is highly regulated.”
The gene targeted in the study appears to regulate neuron development in a similar way in both animals, even though the creatures are eons apart in terms of evolution. So it’s likely that the same gene functions comparably in a broad spectrum of other organisms, including humans, said Olesnicky.
“There’s really a limited number of studies that actually look at what these (genes) are doing in multiple different species,” she said. “We’re really honing in on things that should be relevant to most animals.”
After the husband and wife were awarded a roughly $677,000 grant by the National Science Foundation in 2013, they identified a dozen genes important for neuron development in flies and worms that also have counterpart genes in humans. This study stems from those efforts, Killian said.
The research team included two Colorado College alumni, another UCCS biology professor, and three UCCS students.
Participating UCCS senior Brandon Titus said he used software to trace images of the fruit fly neurons and collect data about their shape. The work was often time consuming and tedious, but learning about the gene’s role made it worthwhile, he said.
“The ultimate reward, for me, is discovery,” he said.
Neurons have thin branches, known as axons and dendrites, that transmit information between the cells. So if one of those branches is abnormal or too short, transmissions may not be able to travel between cells, Olesnicky said.
“Cell shape is just absolutely critical to cell function, and that’s particularly true in the nervous system, where you have circuits that are being built by cells making connections with one another,” she said.
Those with autism or schizophrenia sometimes have neurons with extra branches. Other research has shown that the gene examined in the study might have something to do with amyotrophic lateral sclerosis, or ALS, although a connection hasn’t been proven, she said.
The research lays the groundwork for others, perhaps in the medical community, to pursue a bigger question of whether the specific gene is related to neurological diseases in humans, Killian said.
“We don’t really know that answer,” he said. “We can’t do experiments on humans, but we’ve gathered data that suggests that this is a gene that we might pay attention to as we are learning more about correlating the sequence of the human genome of specific individuals to disease states.”