Studying maggots and mice results in major grants for two professors

Professors Cecilia Flores and Tomoko Ohyama each received international grants worth over $1 million for their innovative studies
Professors Cecilia Flores (left) and Tomoko Ohyama have both recently earned major grants for their respective studies in mice brains and fly larvae

As humans, we may fall into the assumption that we have nothing to learn from the so-called, lower animals in the vast tree of life. And what a mistake that would be, according to Professor Cecilia Flores (Department of Psychiatry) and Professor Tomoko Ohyama (Department of Biology). Indeed, these researchers have both recently earned major grants for their respective studies in mice brains and fly larvae that promise to yield tangible benefits.

Studying effects of amphetamines on the adolescent brain

Flores received over $1.7 million from the National Institute on Drug Abuse of the National Institutes of Health to study the effects of amphetamines on the development of the adolescent brain. These drugs are often prescribed for conditions such as ADHD, but they are also used recreationally, which can result in severe impacts later in life, including psychiatric disorders such as addiction or depression.

Her studies have identified specific genes that are affected by the use of amphetamines and that control the maturation of the frontal lobes of the brain, an area of the brain that is still developing during adolescence. It appears that use of these drugs can alter the expression of these genes, perpetuating the negative impacts of overuse. In addition, she has observed that the adolescent male brain is more prone than the female brain to these detrimental effects of drugs.

“The adolescent brain is highly vulnerable to these stimulants,” Flores said. “However, I want to stress that in dosages used in therapeutic settings, these substances can actually be helpful to brain development. It is not a simple question of not taking them at all.”

The key to all of this can be unlocked through the study of mice she explains. “There is a strong correlation between the developing brains of mice and humans,” she said during a video interview. “Translational research is very important.”

Brain plasticity

Through analyzing the brains of mice at different stages of adolescent development and exposed to amphetamines, her group has been able to determine how these stimulants affect gene expression and, most promisingly, how these affects can be reversed.

“During my graduate studies, I was always impressed by the plasticity of the brain,” Flores explains.

Now, thanks to advances in gene editing technology, this plasticity is something her team is learning to manipulate even more directly. Professor Jeremy Day of the University of Alabama at Birmingham, and co-applicant to her grant, has been experimenting with the use of CRISPR to alter gene expression in brain cells of rodent.

Day has developed a gene-editing tool that will allow Flores’ team to switch off the sensitivity of male mice and make their brains more resistant to disruption by drugs, like their female peers. Although human trials using CRIPSR at not in their program, this research will provide important mechanistic clues to inform prevention and intervention strategies for youth.

“People who are vulnerable still have a chance,” says Flores.

Maggot larva offer insights into our sense of smell

Studying maggots, too, seems to have some intriguing possibilities for humankind. Or so says Professor Tomoko Ohyama. The larva of the humble Drosophila, or the fruit fly, is Ohyama’s chosen canvas which enables her to understand the very fundamental actions that lie behind our reactions to smell.

Her study on understanding this primal sense earned her and her team a $1.25 million grant through the NeuroNex program funded by the FRQ. Launched by the National Science Foundation of the US, the program is a series of highly competitive international funding calls on specific themes, all with the goal of improving our understanding of the brain, both in humans and other species.

“Drosophila larvae have a brain, sensory neurons and a nervous system, just like humans do,” she explained during a video interview. “They respond to sensory inputs much the same as we do.”

Indeed, thanks to this similarity, Ohyama has been able to examine how larvae react to the odours they detect in great detail, with potential implications for human olfactory behaviours. But more importantly, her team can trace the decision-making process that determines how their tiny trainees respond to particular odours, through the use of the calcium indicator, GCaMP.

Proteins like GCaMP, which glow when exposed to light, are used to monitor the activity of specific neurons, showing Ohyama exactly how and when a larva will move when exposed to a smell it can detect.

“Studying how the collective activity of neurons generates innate olfactory behaviour is fascinating,” explains Ohyama. “Because innate behaviour is directly related to the process of evolution, when you observe how neurons respond during such behaviour, you are watching how it evolves before your own eyes.”

But what is the benefit of these observations other than the scientific delight of watching evolution at work? The twist is that Ohyama’s group is one unit of a three-pronged effort. The first unit, which is hers, will study maggots. The second unit, like Professor Flores, will study mice. But the third unit will be looking at applying data from the other two groups to robotics.

Yes, you read that right: robots that can smell. The possibilities are intriguing: robots that can detect dangerous gases for example, and react immediately, or robot chefs that can prepare meals that have wonderful aromas.

While the reader ponders a future of olfactory automatons, Ohyama continues to focus on how animals decide to perform action A or B. But the robotic future described above “is not that far away” she insists. Already, other researchers have been adapting moth antenna to flying drones, a creation known as the “Smellicopter.”

Granting gender gap grows

One future that has not yet arrived is one where women regularly receive the same major grants as their male peers, such as Professors Flores and Ohyama have done. Although the average grant size for men and women academics is comparable, there is still a gap of several thousand dollars per award as shown in an article by University Affairs.

But as grants get larger, the gap grows. This is clear in the even more prestigious Canadian Excellence in Research Chairs program, which awards $10 million to each chairholder. As of 2016, there were 26 chairholders who are men (96 per cent) and only one woman (4 per cent).

Ohyama noted that while there are many women at the post-doctoral level, fewer are Principal Investigators. Flores also noted emphatically: “women can also get the large grants.”