Friday, March 7, 2014

Growing proteins in space

Published in Drug Discovery News

BOSTON—Taking protein-growing to high altitude and low gravity, Emerald Bio has joined an arrangement led by the Center for the Advancement of Science in Space (CASIS) and catalyzed by the Broad Institute of MIT and Harvard to send labs on chips to the International Space Station to study growth of proteins that may help develop treatments for cholesterol and cancer back here on Earth.
Though Melbourne, Fla.-based CASIS has offices in Cambridge, Mass., this is the first time the NASA-selected manager of the International Space Station U.S. National Laboratory has collaborated with the Cambridge-based Broad, according to Brian Hubbard, director of the Broad’s Therapeutics Project Group.
The Broad does work frequently with Emerald Bio, though, and when Hubbard heard last summer that CASIS was interested in growing proteins in space (which had been done before, but not with current technology), he thought of Emerald. “It came together very quickly,” Hubbard tells DDNews, crediting the Broad’s “open collaborative model” with the efficiency. “You don’t need to form a team. The team is already there.”
And it’s a diverse but focused team. In addition to CASIS, Emerald and the Broad, the crew also has NanoRacks of Houston (which has scientific hardware on the ISS) and Protein BioSolutions of Gaithersburg, Md., which recently purchased from Emerald the microfluidic technology that will enable more than 7,000 separate protein-growth experiments to fit in the space allotted on the space station.
“We were actually approached by CASIS … through the Broad,” George Abe, president of Emerald Bio, says. With available time and energy, CASIS was interested in new reasons for growing proteins in microgravity. And CASIS wanted something of real therapeutic value.
Emerald suggested two possibilities: proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene that raises LDL (low-density lipoprotein) cholesterol, and myeloid leukemia cell differentiation protein 1 (MCL1), a key gene in cancer treatments.
Neither structure has “been solved in its empty state before,” Abe said. Protein structures are “extremely sensitive to a lot of environmental factors,” Abe said. “A protein structure will grow or evolve differently in a microgravity environment than on planet Earth.” How they grow when freed from Earth’s gravity could provide new information that will lead to approaches to inhibit relevant genes.
That direct approach is typical of the Broad, Hubbard said. “We’re looking to have real impact on patients but we’re also looking to . . . disruptive technologies” with prospects not today but five to 10 years out, he said. Often, if things aren’t druggable directly, researchers work to find the relevant genes, then proteins and then follow the thread back through gene regulators, eventually finding something that is druggable, he said. But at the Broad, they go for the target itself, even if that means inventing new technology, Hubbard said.
And while the technology itself already existed, the method had to be created to allow this research to proceed. Originally, Emerald had thought it might send the equipment to grow proteins up to the ISS, but that was too big to fit, and too complex to ask astronauts to handle in addition to their other duties.
Instead, Emerald will express and purify the proteins, and then ship them to Protein BioSolutions with protocols for building 36 identical pairs of labs on chips, with each chip holding 200 different configurations of pH, salinity and other environmental factors. The chips will be immediately frozen, with one of each pair sent to the ISS and the other 36 sent to Emerald as controls. (The launch was slated for April as of the writing of this article.)
The chips will be thawed and the astronauts—as well as scientists on Earth—will observe what happens. After about six months in space, the samples will be returned to Earth.
“For any structures that actually grow in space, we will be performing X-ray diffraction on those,” Abe said. And then chemists associated with the Broad will work to identify potential therapeutics that could bind with those proteins, either to prevent their formation, or block or otherwise modify them.
This does not mean that protein production or other aspects of drug development will have to occur in space; rather, it will allow people to discover important information they can use in terrestrial study and production. Nevertheless, this experiment will be a test in another way: of how valuable “a potential market demand for doing early-stage drug discovery work in a microgravity environment” might be, Abe said, noting that this new opportunity could help the ISS remain scientifically and budgetarily viable.