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Novartis, Berkeley sign drug chemistry pact Chemoproteomics and targeted protein degradation could hit previously undruggable proteins Novartis is seeking to broadly expand the repertoire of human proteins its chemists can drug, and it is partnering with the University of California, Berkeley, to do it. The Novartis-Berkeley Center for Proteomics & Chemistry Technologies launched last week to discover hot spots for forming covalent bonds on the surfaces of otherwise undruggable proteins—
Novartis and Berkeley chemists will use automated chemical screening to discover compounds that bind undruggable proteins. those without a clear binding pocket for a drug. Although sometimes these covalent modifications alone can disrupt the protein, the center’s chemists will also design dual-function drugs: At one end they bind a disease-causing protein; at the other end they recruit cellular machinery that tags and ships the protein off to the proteasome, the cell’s garbage disposal. The alliance’s funding amount is unspecified. Its science is squarely in the wheelhouse of Jay Bradner, president of Novartis Institutes for BioMedical Re-
search (NIBR). Before joining Novartis, Bradner was a cofounder of C4 Therapeutics, a start-up that is also developing targeted protein degradation therapeutics. The labs of Berkeley chemists Chris Chang, Tom Maimone, Daniel Nomura, and Dean Toste will house the center. “This is a special collaborative effort,” center director Nomura says. “Novartis is sharing chemical resources that we don’t have.” A recent paper demonstrated the potential of Nomura’s chemoproteomics approach to drug discovery, says John Tallarico, NIBR’s head of chemical biology and therapeutics. Nomura’s team discovered a compound that binds to a colorectal cancer-linked protein called RTN4, which is generally considered undruggable due to its association with the cell’s internal endoplasmic reticulum membranes (Chem. Commun. 2017, DOI: 10.1039/c7cc01480e). “Normally I would say, ‘That doesn’t look possible,’ ” Tallarico says. “It was quite striking how rapidly they discovered it. This is exactly what we’d like to be able to do on a regular basis.” Nomura says Berkeley has been supportive of the industry-academia partnership. It helps that Bradner is an outspoken advocate for sharing scientific discoveries. “There are a lot of Berkeley students involved,” Tallarico says. And although some of the work will be applied to Novartis projects and presumably not be shared, “We also intend to publish work that gets done,” he adds.—RYAN CROSS
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Proportion of industrial chemists who say too much focus on applied research is hindering breakthroughs, according to a survey of 186 chemists by Elsevier. They also say they believe potential chemists choose other fields because innovation in medicine is more associated with fields like biology and because advances in other disciplines get more media coverage.
Activists warn of algae escape The prospects for algae-based biofuel have dimmed compared with a decade ago. Yet a handful of companies are tweaking algae genomes to create more economically viable strains. Ironically, while the aim is eco-friendly fuels, the effort poses environmental risks should the pumped-up organisms escape, activists allege. A report by Friends of the Earth and Biofuelwatch points out that the planet’s native species of algae play an important role at the bottom of the food chain. It cites research showing engineered algae grown in open ponds migrated into the outside environment. Scientists at ExxonMobil and Synthetic Genomics used CRISPR/ Cas9 gene editing to increase lipid production in algae. Biofuelwatch says traits such as enhanced lipid production, improved photosynthetic capacity, and resistance to predators could result in escaped algae that are able to outcompete native species. “Current regulations are abysmally lacking,” says Rachel Smolker, codirector of Biofuelwatch. No regulation can reliably contain an organism that “gets carried in wind, on clothing, out vents, and on the wings of ducks and waterfowl,” she adds. Most algae firms have shifted from biofuels to higher-value products. Sapphire Energy, for example, is developing modified algae for use in animal nutrition. Biofuelwatch says it is monitoring the use of synthetic biology in organisms and plants used to create biofuels. For example, a startup formed by Bayer and Ginkgo Bioworks plans to develop modified microbes that enhance plant growth. The prospect of releasing such microbes in the soil is “very troubling,” Smolker says.—MELODY
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