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Researcher develops technology to advance antibiotic discovery

by Thea Singer

The period from 1950 to 1960 has been called “the golden age of antibiotic discovery,” as half the antibiotics we use today were discovered during that time. Researchers found the new drugs by screening soil for microorganisms that produced compounds lethal to other pathogens. But that well essentially ran dry by the late 1960s, and bacteria acquired mutations that rendered them resistant to the once effective antibiotics.

Enter the iChip, a device developed by Northeastern’s Slava Epstein that could help return us to those glory days.

On Tuesday night Epstein, Distinguished Professor of Biology, will give a talk following the screening of the short documentary The History of Resistance on his contributions to the search for beneficial microorganisms in places as close to home as his own backyard and, perhaps one day, as remote as the planet Mars. The film traces the development of antibiotics from the discovery of penicillin, in 1928, to Epstein’s current investigations with the iChip.

The iChip permits researchers to tap into the untold number of microorganisms that won’t grow under the artificial conditions of the lab. For example, 99 percent of soil-based microorganisms won’t grow there. The iChip isolates and grows individual microorganisms in their natural soil, each in its own small chamber.

“The applications for the iChip are growing,” says Epstein. “One version works better in soil, another in the aquatic environment, a third in the human body, and a fourth in hostile or abrasive settings.” He serves as a consultant on current iChip projects that include the search in China for novel microorganisms in mangroves to harness new metabolites and in Chile for microorganisms that can produce compounds to help plants survive drought.

“Slava is an out-of-the-box thinker,” says Kenneth W. Henderson, dean of the College of Science, who will host the event. “The development of the iChip has transformed our ability to grow previously uncultivable microbes. Breaking this bottleneck has the potential to save countless lives through the development of antibiotics and other pharmaceuticals.”

In 2003 Epstein and Kim Lewis, University Distinguished Professor of Biology, co-founded the Cambridge, Massachusetts-based biotechnology company Novobiotic Pharmaceuticals to accelerate antibiotic discovery using the iChip. In 2015, they and their colleagues discovered teixobactin, a new antibiotic that kills pathogens without encountering resistance. Two additional lead compounds are now in the pipeline: a promising cancer agent dubbed Novo10 and one that targets Mycobacterium tuberculosis, which causes TB.

‘Worlds unimagined’

For Epstein, the iChip is just the beginning. He recently received a National Science Foundation grant to develop the first stage of a far-reaching technology platform called Gulliver that would autonomously find, sort, culture, and analyze microbial species living everywhere from the bottom of the ocean to, perhaps one day, Mars and distant moons.

“All existing technologies that cultivate microorganisms share one element—they require a microbiologist,” says Epstein. “Someone has to take the sample—be it from the gut, the soil, or a marine environment—extract the cells and then grow and manipulate them to learn about the organism’s properties. With Gulliver, no microbiologist is necessary. All of those steps occur onsite, in the microorganism’s natural environment, providing a real-life result.”

Gulliver will be a simple box with membranes for walls. Nanometer size pores will dot the walls. One hole, the “entry pore,” will be larger, its diameter close to the size of a bacterium, about one micron. A researcher will drop the box in the desired location, say, under the sea. The microorganism will travel through the entry pore into the membrane, blocking the entry pore as it simultaneously begins to divide and multiply, forming a chain of offspring that soon populate the box. Naturally occurring nutrients and growth factors will diffuse from the environment into the box, making the conditions inside the same as those outside.

Epstein expects to finish a prototype of the box by the end of 2017. Further work on the project will include building nanosensors into the walls of the box that can measure parameters of microbial growth. Epstein and his team ultimately hope to drop about 1 million boxes, all connected to one another by microfluidic tunnels with valves, to the ocean floor. Each box will contain substances to be tested against the microorganisms. The sensors will relay back, to Epstein’s iPhone, which boxes are showing microbial growth.

But that’s not all, Epstein says. Let’s imagine, for example, that 100,000 of those boxes show microbial growth and you want to know which of the microorganisms can convert cellulose into biofuel. “Using my iPhone, I open the valves and release cellulose into those 100,000 boxes,” says Epstein. “If the microorganism in one of those 100,000 can degrade cellulose into, say, ethanol, the sensor for ethanol will relay that information back to me.”

In Jonathan Swift’s book, Gulliver, you’ll recall, voyages to Lilliput, Brobdinnag, and beyond. Why name the technology platform after him? “It’s going to travel to worlds unimagined,” says Epstein.

The film screening of “The History of Resistance” and the talk by Slava Epstein will take place on Tuesday at 6 p.m. in the Interdisciplinary Science and Engineering Complex Auditorium, 805 Columbus Ave., Boston. Reception to follow.

Originally published in news@Northeastern on March 21, 2017.

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