Creepy-crawly science

They don’t always crawl. Sometimes they scuttle; other times they burrow or buzz. But whether these creepies have six legs or no legs at all, they’re our partners in scientific discovery. Through these invaluable invertebrates, UF Health researchers are learning about the human brain and body, new ways to combat old diseases and how to cure the incurable.

 

Neurodegenerative research takes flight

Diego Rincon-Limas

Diego Rincon-Limas

Diego Rincon-Limas, Ph.D., likens his job to running a hotel — one that feeds and accommodates thousands of guests at a time. However, these guests, each just one millimeter in length, are helping to make strides in the study of neurodegenerative disorders, including Alzheimer’s disease.

Rincon-Limas, an assistant professor of neurology in the UF College of Medicine, leads the only lab on campus studying human neurodegenerative brain diseases in the fruit fly.

“People question if flies even have brains, and are surprised when they hear that they actually have a very sophisticated brain with advanced learning and memory,” he says. “About 75 percent of the genes that are linked to human diseases are also present in the fly.”

The goal of his research is twofold: to identify the molecular mechanisms that trigger neurodegeneration in the fly brain and to discover pharmacological compounds that can stop, delay or prevent diseases like Alzheimer’s and Parkinson’s.

“There is no cure for any of these diseases,” he says. “We know a lot about the proteins that are inducing the toxicity in the neuronal cells, but we don’t know how that happens.”

Rincon-Limas, who has been studying neurodegeneration in fruit flies for about 10 years, says these flexible organisms are also convenient to work with because a single female can lay up to 100 eggs per day, providing hundreds of flies to study.

This is ideal for Rincon-Limas and his team, who have designed special molecules that check if the protein in a cell is well-formed. If these molecules, called chaperones, see a protein that is imperfect, they try to correct the structure of the protein to prevent harmful effects.

The team engineered the chaperones so that they travel outside the cell to meet amyloid beta, the main component of certain deposits found in the brains of Alzheimer’s patients.

“When we produced these engineered chaperones, degeneration was completely stopped,” he says. “It was a very dramatic result in our fly model.”

Rincon-Limas recently received a two-year, $275,000 grant from the National Institutes of Health to begin integrating this research with studies in mouse models. — Emily Miller

 

‘Sea’-ing the beauty in science

When most people think of sea slugs, “beautiful” is not the first word that comes to mind. But for Leonid Moroz, Ph.D., a distinguished professor of neuroscience at the UF Whitney Laboratory for Marine Bioscience, the slimy invertebrates are just that.

Moroz uses the sea slug, also known as Aplysia, to learn more about the human brain. While it’s hard to imagine we have much in common with the marine mollusks, Aplysia and humans share more than 80 percent of genes involved in neurological disorders and memory.

“We need to look at the ocean as a source of unique solutions and innovations for neurological medicine,” says Moroz, who has been studying brains, neural circuits and behaviors for more than 30 years.

Sea slug brains are easy to study, he says, because they have the largest neurons in the animal kingdom. Even more remarkable, he adds, is the aesthetic beauty of these neurons, which come in shades of orange, yellow, white, red and in some species, green.

The goal of Moroz’s research is to reconstruct fully operational neural circuits and to use this knowledge to reverse neurodegenerative processes — and potentially cure age-related memory loss. This is a unique goal, as it focuses on stopping and reversing the degeneration as opposed to slowing it down.

“This research means a lot for regenerative medicine because a majority of neurological disorders are one-way tickets, meaning we often are working on therapies to slow down an already ongoing degeneration process,” he says.

Employing the sea slug and comb jellies (another group of marine invertebrates), Moroz is working to develop new methodologies that allow researchers to identify and quantify gene activity in a single neuron as the neurons learn and remember in real time. He also hopes to identify new molecular targets for therapies.

“But most important at this time is our understanding of how so many genes and thousands of regulatory RNAs act together to form a memory trace and keep such memories, like that of your fist kiss, for the rest of your life,” he says. — Emily Miller

 

More than just a parasite

Nematodes are simple creatures, with only 959 cells to their name compared with the trillions that humans have. Despite this, their genetic codes and metabolism are similar to ours — making nematodes, also known as roundworms, a useful tool in understanding the human body.

Nematodes, which can be free-living or parasitic, are believed to account for four out of every five animals on Earth. These often-microscopic worms have unsegmented, cylindrical bodies and include species such as the hookworm, pinworm and heartworm.

“They make a major impact on the world, but we just don’t see them because they are usually so small — even though they are around us in many different environments, including the soil, all the time,” says Art Edison, Ph.D., a professor of biochemistry and molecular biology in the UF College of Medicine who has been working with nematodes for 20 years.

His studies of nematodes have led Edison to his latest work with the Southeast Center for Integrated Metabolomics at UF. Metabolomics is the study of the presence and organization of metabolites, products of the metabolism that are present in organisms, cells and tissue.

Through a five-year, $9 million grant from the NIH, Edison and team members will help other investigators study diseases such as cancer or muscular dystrophy by applying some of same metabolomics methods originally developed using nematodes.

Because nematodes are easy to manipulate and work with, Edison and colleagues can develop new methods to observe metabolites and establish protocols, he says. Many of these methods can be applied to any organism, including humans.

“It’s more global metabolomics,” he says.

Through the center, Edison and his colleagues will soon begin to offer metabolomics services to other groups in biomedicine, agriculture and biology. — Kelsey Meany

 

Bloodsuckers from North Florida

Rick Alleman

Rick Alleman

To most people, they’re disease-spreading, bloodsucking pests, but to Rick Alleman, D.V.M, Ph.D., they make his research … well, tick.

For years, Alleman, a professor of physiological sciences at the UF College of Veterinary Medicine, has been studying the prevalence and spread of ticks and tick-transmitted infections in North Florida. In his most recent study, Alleman and graduate student Katherine Sayler have tested the parasite’s spread of bacteria in white-tailed deer, specifically the Lone Star tick.

“It’s of public significance to look at the prevalence of bacteria within these ticks that can cause disease in people and pets,” Alleman says. “The Lone Star tick is of interest because in North Central Florida and all throughout the Panhandle, it’s the most prevalent tick species. It’s also one of the more aggressive ticks known in the entire area.”

In 2012, Florida had 47 cases of tickborne infection — more than Maine, New York, Pennsylvania, North Carolina, Rhode Island and Wisconsin combined, according to the Florida Department of Health. Alleman says confirmed cases are just a small percentage of the actual number of people who are exposed at different levels. Ticks can carry a wide variety of diseases such as Lyme disease. The Lone Star tick also carries the bacteria that causes ehrlichiosis, which can be fatal if not treated properly.

So what’s a North Florida-dweller to do to keep pets and people safe? Alleman suggests checking for ticks on your body, and your pets and children, whenever in a rural area where ticks are prevalent. If you find one, it’s important to remove it within 12 to 24 hours, before disease can enter the body. Grab underneath the tick’s body with tweezers, the fingers or a commercial tick-removing device and pull it off without squeezing; squeezing can release more of the tick saliva, which can introduce bacteria into the skin.

“When you engage in outdoor activities, check yourself, family members and pets for ticks — whether you’re hiking or camping or jogging,” Alleman says. — Kelsey Meany

 

The “yuck” factor

Ancient peoples used them to clean wounds. Battlefield surgeons used them to treat amputated limbs. In the 1940s, penicillin was introduced and with the increased use of antibiotics, they fell out of favor. Only now they’ve returned to modern medicine, more refined, to take on antibiotic-resistant bacteria and chronic wounds. What are they? The answer may make your skin crawl.

Three years ago, Linda Cowan, A.R.N.P., Ph.D., a wound specialist for the North Florida/South Georgia Veterans Affairs Health System, convinced Gregory Schultz, Ph.D., director of the UF Institute for Wound Research, to investigate the effectiveness of maggot therapy. Now the team has published research showing how effective medicinal larvae are in the fight against bacterial infections.

A chronic wound is an injury to the skin that fails to heal after approximately two months due to conditions such as diabetes, poor circulation or immunosuppression. A layer of microbial slime called biofilm forms in the wound and produces its own protective coating, which keeps it from healing. Our immune system is ineffective at killing these microbial colonies; fortunately, medicinal larvae are not.

Enter larval debridement: the removal of unhealthy and infected tissues using maggot therapy. During this procedure, up to 100 or more medicinal larvae are placed into the wound and covered with a dressing that keeps them from crawling out. The larvae then consume the biofilm and dead tissue without eating healthy flesh.

Some patients who underwent this treatment reported having a “wiggly sensation,” says Schultz. Even so, he says the maggots are a far less painful option than scraping their wound with a scalpel — an alternative for removing biofilm.

“When you treat with larvae for one day, it kills 99.999 percent of the biofilm,” says Schultz.

It may also be comforting to know that these larvae are not your typical infantile flies. They are a specially grown species of the green bottle fly that are completely disinfected and sterilized, as required by the U.S. Food and Drug Administration. Using a special dressing (like a tea bag) is another way Schultz and Cowan hope to combat the “yuck” factor.

BioMonde, the European larval debridement manufacturer that is funding Schultz and Cowan’s research, is moving to the Florida Innovation Hub in Gainesville in 2014. Within this facility, the researchers will continue their clinical assessments of larval therapy. — Nicole Zakrzewski

 

Biting back against malaria

Malaria has been on his mind for 14 years. It all started at the Kenya Medical Research Institute, where research officer Bernard Okech, Ph.D., decided to focus his research on Anopheles gambiae, a mosquito with a bad reputation — as Africa’s primary and most efficient carrier of malaria, a disease that kills over half a million people each year.

Today Okech, a research assistant professor in the UF College of Public Health and Health Professions, continues to study malaria and other diseases transmitted by blood-feeding insects.

“At the end of the day, what we want to do is reduce the risk of getting malaria,”

Okech says.

Okech is particularly interested in tryptophan, a common amino acid that is essential for mosquito larvae growth. Interfering with larval tryptophan absorption using inhibitors that specifically target tryptophan transporters could potentially be a powerful control measure for mosquitoes.

Additionally, Okech studies anti-malarial drug resistance and the bioecology of mosquito-borne diseases in Haiti.

“Haiti is one of those countries with very poor public health infrastructure, but where I think malaria can be very easily eliminated,” he says.

Okech began research in Haiti in 2009, and two years later UF established a public health lab in the country — funded in part by a U.S. Department of Defense award granted to Okech. The lab processes samples before shipping them to UF for further research.

“Malaria is a treatable disease that can be eradicated, and there are very serious efforts currently underway to achieve this,” Okech says. “Our research is uncovering new findings every single day that add to our knowledge in the fight against malaria.” — Nicole Zakrzewski

 

 

 

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