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Looking at Human Neurological Disorders through Fruit Fly Eyes with Dr. Rincon-Limas

By Patrick Sherry

Diego E. Rincon-Limas, Ph.D., Associate Professor in the Department of Neurology, uses fruit flies to create models of neurodegenerative diseases common in humans by mimicking their pathology. Through this model organism, Dr. Rincon-Limas attempts to identify key mechanistic roles that specific genes have in causing and progressing neurological diseases.

Drosophila melanogaster, the common fruit fly, is a ubiquitous species with a relatively simple genome. Fruit flies have a short lifespan, reproduce quickly, and have about 75 percent of genes responsible for human disease making them a valuable resource for genetic research. However, Dr. Rincon-Limas is one of the few labs that use this species at the University of Florida. Particularly in neurological diseases, researchers like him use a variety of methods to study the pathology of genes that cause and influence diseases – one of the most apparent being the use of the eyes of fruit flies to show causality. In essence, the eyes are the window to scientific inquiry.

Photo courtesy of Dr. Rincon-Limas. The different reactions to certain proteins and genes create disruptive patterns in the eye that can show the function of specific genes.

“The nice thing about [the eyes] is that we don’t need to do any dissection on the fly because you can observe [it] under a microscope,” said Rincon-Limas. “This is good because we can use the eye of the fly as a platform to do genome-wide screening in a relatively short period of time.”

To investigate which genes of interest influence human disease, transgenic flies are generated. Once these are complete, a neurotoxic protein associated with a specific disease is activated in the eye. Fruit fly eyes have hexagonal arrays of tiny structures called ommatidia, which react in different ways to distinct protein or gene activation. This gives visible, informative results to the specific pathological role of certain genes. Validation from eye examination then leads to targeting other organs such as the brain where further investigation can be done on how these select genes impact a variety of neuronal functions, such as learning, memory, or locomotion. This also provides the potential for discovering drugs and therapies for these diseases.

“The eye of the fly is a very useful way to take a look into neurodegenerative processes in humans,” said Rincon-Limas. “It is a very simple, direct, useful, and reliable way to take a quick look, first insight into what’s going on.”

One of many reasons Dr. Rincon-Limas pursues research into neurodegenerative diseases is his personal experience with them. His father’s memory vanished gradually due to Alzheimer’s disease and like so many others, he had to undergo the several trials and tribulations of having a loved one live with a disease that has no cure. From this, he shifted his focus from the developmental biology of wing formation in flies to the increasingly accelerating field of neurodegenerative diseases. Due to this, he could use his skills to push scientific understanding toward these arcane topics.

Photo courtesy of Dr. Rincon-Limas. Dr. Rincon-Limas can activate genes or cause reactions in flies by including certain drugs within the food fed to fruit flies.

“It was a critical moment in my life because [it was] a time to see what can I do to use my knowledge to help in this field,” said Rincon-Limas. “And little by little, I started to incorporate more fly models of these diseases.”

Furthermore, despite this disciplinary shift in his career, Dr. Rincon-Limas considers himself a “Fly Whisperer” as he uses flies and their behavior to uncover the hidden truth behind the causes of neurological diseases. His lab has been able to be one of the few that investigates over 10 neurodegenerative diseases and related disorders and continues to add more pursuits to this list. Moreover, he finds the opportunity to teach the future generation of scientists as a rewarding experience because he is able to show them his passion and the innovative field of scientific research.

“Follow your passion,” said Rincon-Limas. “You don’t need to have a background [in a disease] if you are an undergraduate. Ph.D. student, or a postdoc. I was following my passion – that’s what I always tell students: follow your passion. Passion is what drives progress, it’s critical, and it’s the number one factor to be successful.”

Surprisingly, considering all these accomplishments, he partially believes that he makes strives in his research due to his love for fishing. Fishing is an opportunity for escape and relaxation, and he uses it as an outlet to refine ideas and engage in healthy thinking about what could be next.

Photo courtesy of Dr. Rincon-Limas. Dr. Rincon-Limas teaching the genetics of fruit flies. The species has about 100,000 neurons and a brain the size of a poppy seed.

But overall, he emphasizes that fruit flies are the main reason for his success. They provide him with the tools to further scientific understanding and pave the way for discoveries to help people affected by these diseases.

“Knowing that you have a model that is flexible, versatile, and highly appropriate for all these discovery initiatives makes me feel that I have a moral responsibility to do something and to teach the next generation in Drosophila genetics,” said Rincon-Limas.