October 9, 2018
BIOSCIENCE NOTEBOOK

UConn licenses IP to New Haven's Biohaven

UConn has authorized New Haven's Biohaven Pharmaceutical Holding Co. Ltd. to study and develop an antibody it developed that fights autoimmune disorders.

Connecticut's flagship state university says it signed a license agreement to provide Biohaven intellectual property rights to develop the antibody UC1MT, which targets extracellular metallothionein (MT), a stress response protein that has been shown to develop autoimmune and inflammatory diseases.

The university and Biohaven also signed a collaborative research agreement to continue exploring the role MT plays.

Under the license agreement, Biohaven is granted exclusive acquisition rights for a worldwide license of UC1MT and its patents for development and commercialization throughout the world.

The antibody was discovered by professor Michael Lynes, UConn's department head for molecular and cell biology.

Lynes said the agreement is a "critical" step for his research group in their effort to "define the path for taking our basic research discoveries into the clinic."

"I believe we have an exciting opportunity to develop this new approach to the management of important inflammatory and autoimmune diseases where metallothionein plays a significant role," he said.

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By dramatically reducing the therapeutic effects of antibiotics, the formation of organized groups of bacterial cells known as "biofilms" can be deadly during surgeries and in urinary tract infections. Now Yale researchers are closer to understanding how these biofilms develop, and potentially how to stop them.

Biofilms form when bacterial cells gather and develop structures that bond them in a gooey substance. This glue can protect the cells from the outside world and allow them to form complex quasi-organisms.

Biofilms are found in many environments, including unwashed shower stalls or lake surfaces. Because their protective shell can keep out treatment agents, biofilms are most dangerous when they invade human cells or form on sutures and surgical catheters. In U.S. hospitals alone, thousands of deaths are attributed to biofilm-related surgical-site and urinary-tract infections.

"Biofilms are a huge medical problem because they are something that makes bacterial infections very difficult to deal with," said Andre Levchenko, senior author of the study, published Oct. 5 in Nature Communications.

Fighting biofilms has been problematic because it hasn't been well understood how bacteria cells transition from behaving individually to existing in collective structures. However, researchers in Levchenko's lab, working with colleagues at the University of California/San Diego, have discovered a key mechanism for biofilm formation that also provides a way to study this process in a controlled and reproducible way.

The investigators designed and built microfluidic devices and novel gels that housed uropathogenic E. coli cells, which are often the cause of urinary tract infections. These devices mimicked the environment inside human cells that host the invading bacteria during infections. The scientists found that the bacterial colonies would grow to the point where they would be squeezed by either the walls of the chamber, the fibers, or the gel. This self-generated stress was itself a trigger of the biofilm formation.

With this discovery, said Levchenko, the John C. Malone Professor of Biomedical Engineering and director of the Yale Systems Biology Institute, researchers can use various devices that mimic other cellular environments and explore biofilm formation under multiple environments and circumstances. They can also use the devices introduced in this study to produce biofilms rapidly, precisely and in high numbers. This may allow screening drugs that could potentially breach the protective layer of the biofilms and break it down.

"Having a disease model like this is a must when you want to do these kinds of drug-screening experiments," Levchenko said. "We can now grow biofilms in specific shapes and specific locations in a completely predictable way."

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