See inside KC labs where fish regrow their hearts, research ‘sounds like science fiction’

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Tens of thousands of zebrafish capable of regrowing their hearts and thousands of snails that can regenerate their eyes are being cultivated at a Kansas City institute — laying the foundation for future cures to human diseases.

The Stowers Institute, situated next to the University of Missouri - Kansas City’s campus, is the center of 21 different research labs, each seeking answers to medical and biological mysteries.

Several focus on species that can regenerate, which means they can regrow part of their bodies. The phenomena have human implications when it comes to aging and conditions like spinal cord injury and macular degeneration, which causes vision loss.

“What we’re trying to do at the Institute is to try to identify what the actual molecular and cellular mechanisms are that these organisms deploy in order to execute or carry out these functions,” said Alejandro Sánchez Alvarado, president and chief scientific officer.

The Institute is well-positioned to take on such a challenge. A host of problems have resisted scientific advances because there aren’t many organizations that want to pour resources and time into finding solutions.

“That’s a distinguishing attribute of the Stowers Institute, is that we’re allowed to take those risks, we’re allowed to have the resources and the people to actually go after these very, very difficult problems without the guarantee of success,” Sánchez Alvarado said. “That’s very uncommon.”

The Institute was established in 1994 by James Stowers, who founded American Century Investments, and his wife Virigina Stowers. Forty percent of ACI’s profits go to the Institute, a unique structure which removes the need for outside funding and grants.

In Sánchez Alvarado’s 13 years with the Institute, scientists have made major discoveries including identifying a cellular agent responsible for regeneration in an organism and figuring out what cells will become what type of tissue in a genome.

In an experiment with fruit flies, they found out that some plaques help restore long-term memory. Build up of plaque in the brain is thought to be associated with diseases like Alzheimer’s and Parkinson’s. They want to see how the structures of good and bad plaques differ so that pharmaceutical treatments can attack the harmful type.

The work has to be rigorous and reproducible.

“This work is labor intensive, it is time intensive and for the most part, thankless because nobody really understands what we are doing,” Sánchez Alvarado half-joked.

Inside the labs

Laboratory manager Carrie Carmichael takes care of about 35,000 zebrafish in a lab filled with rows of small tanks. They are getting ready to expand capacity to about 50,000 fish. Zebrafish can regenerate their fins and hearts. They are great for imaging, she said, because you can watch their cells divide.

The Stowers scientists closely study these processes in animals to learn more about how they could apply to human conditions.

Hundreds of apple snails — which can regrow their eyes in about 20 days — dawdle around large tanks in another lab. Like humans, snail eyes have a lens, retina and cornea.

Carlos Barradas, a pre-doctoral researcher, said the team he’s on is looking at how the snails’ nervous systems influence regeneration. Some of the snails, originally from Brazil, have modified genes. The lab has about 1,200 adult snails at any given time and possibly as many young snails that haven’t reached reproductive maturity.

Planarians, or flatworms that live in salt or freshwater, regenerate like crazy, Sánchez Alvarado said. There are about 8,000 species, so they had to choose one. Criteria was based on having a small genome to sequence, a small number of chromosomes, if it’s easy to rear in the lab, and how easily it reproduces.

One species that fit the bill was discovered in an aquifer in Spain in the 1970s. Sánchez Alvarado obtained them in 1998 after planting traps in fountains in Barcelona and brought them to Kansas City when he joined the Institute in 2011.

Their labs now have hundreds of thousands of planarians, which originated from a single one. The organisms range in size from a speck to about a centimeter.

Shane Miller, head of aquatics, said Stowers is the epicenter for that species. They send some of them to more than 30 other research institutes.

The flatworms in the tanks are in different phases or are different strains. Once they grow big enough, they split themselves into two, creating two separate organisms, said laboratory manager Rachel Livella. Lab employees feed them beef liver.

Steph Nowotarski is head of electron microscopy where she uses electricity to image animals. The technology provides a better resolution. A photo of a planaria can help scientists find where the nuclei is, and 3D data helps them understand what is going on in a cell.

She said humans aren’t so different from flatworms. But stem cells make up about 20% of a planaria and only about 1% in humans.

Sánchez Alvarado said the Institute is trying to understand why regeneration is “so unevenly distributed in the natural world.” In other words, why some organisms are capable of regrowing body parts while others are not.

It is also working to establish a lab for jellyfish that exhibit the “Benjamin Button” effect of reverting back to earlier stages of development.

“If you had told me 13 years ago that we’d be doing the work today, I would say what are you drinking because that sounds like science fiction,” he said.

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