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LANL scientist testing bacteria to stop diseases

LOS ALAMOS – A Los Alamos scientist is assembling a growing team of international experts to test his biotechnology for attacking vector-borne diseases.

Richard Sayre

Richard Sayre

Richard Sayre, a top-level senior research scientist at Los Alamos National Laboratory, is also chief scientific officer of Pebble Labs Inc., which he helped create last year along with investors interested in his ideas for preventing the spread of viral diseases like Zika that live in mosquitoes – and doing so without killing off the bug.

Now he’s brought on four international research scientists and two technicians from around the globe who specialize in various areas of biology to use Sayre’s technology to prevent both mosquito and plant diseases. The first full-time researcher came on in November and the latest arrived last week. In the next few months, he hopes to have a team of 12 with all types of expertise to work on both types of organisms as they prep for the next steps toward getting the technology approved for commercialization.

The science that the group is experimenting with creates genetically engineered bacteria that, once consumed by mosquito larvae, stay in the insect’s gut. It can also live in plants.

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Inside the bacteria is a strand of double-stranded RNA, which is typically a single strand. The organism, an insect or a plant, then breaks down double-stranded RNA into small single-stranded, or small interfering, RNA. If the result is a complete match with messenger RNA from a gene that is vital to a certain disease, the two strands will bind together. An enzyme will recognize that bond and degrade, or “turn off,” the messenger disease RNA, Sayre said.

“It’s really interesting in terms of research, but also contribution: how do you contribute to society as a scientist?” said Pedro Miguel Melo da Costa Nunes, a Portugal native and RNA interference expert, when asked why he joined Pebble Lab.

He and his new colleagues have a workspace at a biolab and greenhouse at the New Mexico Consortium, a shared space where they try to identify a pathogen’s DNA sequence in order to identify an RNA match.

Kimberly Harrison

Kimberly Harrison

The consortium is a LANL-associated nonprofit that created its laboratory shortly after Sayre began working at the lab in 2011, to give scientists with startups a place to work without having to invest in equipment, said Consortium CEO Steven Buelow. Pebble Labs and employees for two of its sub-companies, LittleFly for mosquitoes and IronLeaf for plants, have a joint-employment deal with the consortium. Pebble Labs chief development officer Kimberly Harrison said the arrangement allows the Pebble group to attract the “best of the best” among world experts. The researchers have access to health insurance and other employee benefits through the consortium while working with Sayre.

 The multinational team of scientists at Pebble Labs include, from left, Konstantinos Lymperopoulos, Cynthia Sockos, Pedro Miguel Melo da Costa Nunes, Tatiana Vinogradova-Shah and Guohau "Karen" Yin

The multinational team of scientists at Pebble Labs include, from left, Konstantinos Lymperopoulos, Cynthia Sockos, Pedro Miguel Melo da Costa Nunes, Tatiana Vinogradova-Shah and Guohau “Karen” Yin.

Most of Pebble’s other full-time research scientists – including virologist Konstantinos Lymperopoulos, originally from Greece; Russian cell biologist Tatiana Vinogradova-Shah; and plant biologist Karen Yin, originally from China – also said they joined up to be a part of research that could directly impact people’s lives, especially at a time when the world faces the spread of certain diseases.

Climate change that allows bugs to migrate north and globalization that makes it easier for humans to travel from one place to another, Sayre said, has helped spur the “rapid emergence” of viruses like Zika in the Americas.

According to the Center for Disease Control, Zika is passed through the Aedes mosquito, as well as through sexual transmission and from mother to fetus during pregnancy, which can cause serious birth defects.

Sayre’s mosquito team is directly trying to address the spread of that vector-borne disease, as well as others like dengue and yellow fever.

Guohau "Karen" Yin grows arabidopsis plants for testing at Pebble Labs in Los Alamos

Guohau “Karen” Yin grows arabidopsis plants for testing at Pebble Labs in Los Alamos.

“(This technology’s abilities) keeps the risk of epidemic or pandemic at its source,” said Harrison, who added that diseases nowadays are “flourishing at an unexpected rate.”

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As the parents of a son who contracted dengue as a teenager, she and her husband, Pebble Labs CEO Michael Harrison, had a particular interest in vector-borne diseases. She approached Sayre with interest in supporting his research after seeing his previous studies and patents related to disease control for fish and shrimp.

Sayre received permission from LANL to take his latest advances out of the lab and build a startup with investors, whose interests include working with agricultural companies to get the disease-fighting bacteria sold in a spray form for use in gardens or other areas.

While concerns have been raised about genetically modified organisms, or GMOs, Sayre said RNA molecules are “naturally occurring in all living organisms” and are considered safe when attacking the correct gene target. Also, he said, the molecules are non-allergenic, unlike proteins that are modified.

Because the bacteria is natural, mosquitoes or plants would be able to survive with the bacteria living inside it.

“We’re not introducing anything foreign … this way, we can save the host, we don’t kill them,” said Lymperopoulos, who moved his family, including his two children, to Los Alamos from Germany earlier this year. “From an ecological point of view, but also from an ethical or moral (one), it’s very important.”

The modified bacteria on mosquitoes is created in-house in Los Alamos using a fermenter, but it’s sent to be tested on insects in labs at New Mexico State University and Colorado State University, both of which have teams collaborating with the startup.

The way the bacteria is created makes the biotechnology transferable to plants and animals, said Sayre, as long as researchers can identify a right gene and its DNA sequence.

“It’s sort of cookie-cutter,” Sayre said of the technology. “Once you have it optimized for your particular host organism (and) when a new disease comes along, the only thing that you need to change is the double-stranded RNA.”

Currently, Sayre and his team are working toward “proof of concept” to show they have stopped a mosquito from spreading viruses. Once they prove the bacteria is effective, which Sayre expects in the next few months, the team will need to seek approval from the Food and Drug Administration for outdoor field trials with the help of NMSU and CSU. He said the company is already in consultation with the FDA.

The double-stranded RNA method has been around for ages, Sayre said. The missing piece was how to safely bring it to a host. The team considers their consumable bacteria and double-stranded RNA a more “sustainable” approach compared to other methods that have tried to stop the spread of Zika through “gene-drive” technology, which sterilizes males in hopes that a specific disease-carrying bug population will die off.

Sayre said the sterilization approach, which he referred to as “playing God” with a species’ existence, raises many issues. Other types of mosquitoes, ones that can live in a larger variety of weather conditions, including drought, could acquire the ability to spread the disease and make it more widespread. In areas like South America, one country could approve extinction methods, while another country may not.

“We’re not altering and driving species to extinction,” he said of the Pebble Labs approach. “We’re not interfering with their ecosystems and we’re not creating a niche for something else to move in that might be worse.”


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