All posts by: Sarah Hansen, M.S. '15

UMBC biologists Phyllis Robinson and Preethi Somasundaram may have identified a key factor that contributes to our understanding of biological clocks and associated disorders, such as non-24 and seasonal affective disorder. Their new research focuses on the role of melanopsin, a retinal protein, in aspects of unconscious vision that regulate the biological clock.

Unconscious vision, or non-image-forming vision, is an often-underappreciated function of the eyes. While we look around, our eyes are doing more than processing what we consciously see. Specialized cells in our eyes also constantly send messages to the brain that regulate our circadian rhythms, sleep patterns, pupil size, and even our mood. One of the brain areas these messages head to is the superchiasmic nucleus (SCN), which Robinson, professor of biological sciences, calls the “master clock.”

“The SCN controls a lot of physiological functions,” Robinson explains, “from appetite to the ability to do math.”

For our internal clock to work, the specialized cells must effectively respond to light, sending messages when light is present and turning off when things go dark. Robinson and Somasundaram have found that a modified version of melanopsin in the cells can result in messages continuing to be sent long after the lights go out, which affects various behaviors. In other words, broken melanopsin breaks our bodies’ master clock.

For her dissertation, Somasundaram, a Ph.D. candidate in biology, tested how mice’s pupils reacted when she exposed them to a flash of light and then placed them in darkness. The normal response in any mammal is for the pupil to constrict upon exposure to light and then dilate again in darkness. This reflex is important to protect the retina from damage caused by excessive light, and it allows us to see consistently under varying light conditions. In Somasundaram’s experiments, mice with normal melanopsin and modified melanopsin both constricted their pupils similarly when shown a flash of light, but it took the mice with modified melanopsin almost 100 times as long to dilate their pupils again in the dark—9.5 minutes compared to 4.6 seconds on average in normal mice.

“When you think about signaling,” says Robinson, “you want the signal to turn on when it detects something, but then turn off so it can detect something else.” By taking nearly 100 times as long to turn off, the broken melanopsin doesn’t transmit any new input to the brain during its extended “on” period, which affects behaviors that rely on that information.

Somasundaram also tested the effect of melanopsin on a longer time scale by looking at jet lag. She exposed the mice to an artificial time change of six hours (similar to flying from Amsterdam to New York). The mice with normal melanopsin took 5.6 days to adjust their activity to the new cycle, but those with broken melanopsin adjusted in just 2.8 days on average.

These two dramatic results, both shown for the first time in an animal, demonstrate that melanopsin plays a major role in clock-driven behaviors. If it turns out that human patients with clock-related disorders have the same kind of modification in melanopsin as Somasundaram’s mice, that would suggest further melanopsin research could eventually lead to treatments for these disorders.

Melanopsin is found in five subtypes of the specialized cells that regulate unconscious vision. Somasundaram’s work only tested a subset of them, so she and Robinson are now looking ahead to using CRISPR (a new, more realistic genetic modification technique) to test the other subtypes for melanopsin’s possible effects on behaviors like sleep and learning. This future research was just recently supported by a five-year grant from the National Eye Institute.

Many currently prescribed medicines target the class of proteins that melanopsin belongs to, but, Robinson explains, “There aren’t any drugs on the market that I know of that target the turn-off mechanism for melanopsin.” If melanopsin turns out to be the culprit behind biological clock disorders or behaviors like insomnia, that could change.

Photo by Alessandro Lorizzo, used under CC 2.0 license.

Michelle Starz-Gaiano’s research on fruit flies seeks to uncover biological mechanisms driving embryonic development and is applicable to a variety of contexts. For example, her findings may help scientists and doctors better understand how cancers metastasize, leading to more effective treatments.

Starz-Gaiano, associate professor of biological sciences at UMBC, just received a three-year National Science Foundation grant to pursue research on a step in early fly development when a small cluster of cells migrates from one end of the developing egg to the other. While scientists have long understood that the process is driven by a chemical gradient—a higher concentration of a chemical signal at one end of the egg than the other—Starz-Gaiano thinks migration is more complicated than current models predict. “I don’t think the signaling molecules are where we expect,” she says.

The developing egg is bounded by follicle cells, with polar cells at each end of the egg. During early development, a cluster of these cells migrates, which is critical for normal development. This step is similar to metastasis, the process cancer cells undergo when they detach from a tumor and travel through the bloodstream.

In previous studies, Starz-Gaiano was surprised to find that the cells intended for migration did not form in the egg boundary symmetrically. That suggested that they were not uniformly receiving the protein that signaled migration.

Starz-Gaiano hypothesized that the cells beneath the polar cells were not in fact like dice laid end-to-end, with no spaces, as some scientists presumed. Instead, they were more like marbles, creating clefts between cells where the signal molecule could be trapped, therefore altering the selection of migrating cells and the start of the cell migration process.

Starz-Gaiano and collaborator Brad Peercy, associate professor of mathematics at UMBC, built a computer model to simulate the marble-like arrangement. Sure enough, the model recreated the asymmetrical cell pattern Starz-Gaiano and her students saw in real fruit flies, a result they published in 2015.

To validate the computer simulation, Starz-Gaiano’s new research calls for extensive imaging work with another collaborator, Tagide deCarvalho, director of UMBC’s Keith R. Porter Imaging Facility. Their goal is to identify individual signaling proteins within the egg to see if pools show up in the spaces between cells.

The standard cell migration model also ignores the fact that there are a lot of other cells in the way as the migrating cell cluster travels from one end of the egg to the other. This cellular obstacle course affects the migrating cluster’s path and speed, as well as the location of the signaling molecules throughout the egg. “The tissue landscape may be influencing signaling in ways we’re not appreciating,” says Starz-Gaiano.

The series of chemical reactions that controls cell migration in Starz-Gaiano’s fruit flies is markedly similar to what happens in other animals, including humans, so “it’s the perfect system for exploring this idea,” says Starz-Gaiano.

Starz-Gaiano points out that the passage of drugs through the body is likely also influenced by the structure of surrounding tissue. Understanding how surrounding cells affect the course drug molecules take through the body could lead to drugs that interact more actively with the blood vessels and organs they pass through, possibly increasing the amount of the drug that reaches the target, reducing required dosage and side effects.

Starz-Gaiano is excited to get started on the new project. Though challenging, it has the potential to create a paradigm shift in the cell signaling field. “It was a vote of confidence to be recommended for the grant,” Starz-Gaiano says, “and I can’t wait to get the answers.”