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Van der Donk cites one example that’s already made a difference. Many enzymes—proteins that carry out chemical reactions—do their job by breaking a few bonds and creating a few others. Energy is transferred from bond to bond to rearrange a compound. This means that to build a large compound from raw elements—either inside a cell or by industrial chemists in a lab—many chemical reactions are often needed. Each reaction shifts a few bonds, gradually building the desired molecule.
But some enzymes in cells are more efficient, carrying out many bond rearrangements at once. Chemists have used these enzymes as inspiration to design enzymes for industry. “This can make drug synthesis, or material synthesis, more efficient and cheaper,” says van der Donk.
And sometimes it’s not learning directly from cells but being inspired by a biological problem that drives chemistry forward. Schreiber calls it “next-generation synthesis.” It’s the idea that chemists faced with a difficult biological problem sometimes have to create new chemical methods to solve it. Schreiber, for example, developed a way to generate compounds with the ability to modulate biological processes not otherwise possible. His method, called diversity-oriented synthesis, allows scientists to discover chemicals that target, for example, proteins that cause human disease.
“In the same way that next-generation sequencing is transforming genetics, next-generation synthesis is transforming molecular biology,” says Schreiber.
Learning to Cross Boundaries
While some chemists dive into postdocs or other training opportunities focused on biology to help round out their own lab’s work, others stay specialized in chemistry and collaborate with biologists. Neither path is easy. But with the right navigation, both routes can lead to success.
For those who want to collaborate, the key is understanding what each field has to offer. Carolyn Bertozzi, an HHMI investigator at University of California, Berkeley, believes that biologists and chemists have different motivations. Bertozzi, whose lab has used chemical methods to track sugars within cells, has mentored both biology and chemistry students (see Perspectives & Opinions, “Changed Expectations”).
“Biologists are very problem oriented,” she says. “They often get frustrated if they can’t solve the problem they want to solve. But chemists like developing new technologies, even if it doesn’t get to the heart of a problem. It’s still a success if it works.” As a mentor, Bertozzi tries to help biology students see that their work can be successful as long as it leads to a discovery. For chemistry students, she pushes them to take greater responsibility when tackling an applied problem. “I want them to think about what biological questions cannot be answered using current methods and to focus their creative energies on technologies that really address that need,” she says.
These days, even a chemistry student who wants to stay focused on chemistry often works in a biology lab to get a feel for how to work with biologists, according to Schreiber. “You’ll join a project where next to you, elbow to elbow, may be a developmental biologist trying to differentiate a cell, and on the other side is a computer scientist trying to convert data to knowledge,” he adds.
This won’t necessarily teach chemists everything about developmental biology, or everything about computer science, but it will teach them how to work with those scientists. “The chemist simply needs to know what those fields are capable of achieving,” says Schreiber, “and how it connects back to their own skill set and discipline.”
Crabtree’s biology lab frequently hosts chemistry postdocs. “Occasionally these students do actual chemical synthesis,” says Crabtree. “But mostly they’re there to learn biology. And I always hope they come away with an appreciation for what happens when you bring together the tremendous power of genetics with the tremendous power of chemistry.”
Biologists too, are gaining an appreciation for how chemistry can help them, says Crabtree. “When you begin with a biological process that you want to understand,” he says. “One of the first questions you can now ask is, ‘Is there a chemical that prevents this process?’ And if not, ‘Can it be synthesized?’” Such a question can launch career-changing collaborations, as Crabtree and Schreiber have learned.
“The important thing,” says van der Donk, “is that biologists and chemists are really talking to one another more than we used to. As a result, biologists understand better what chemists can bring to the table. And chemists understand better the questions that biologists really care about.” This, he says, has led to a bigger impact of chemists on biological problems. And they’ve only just begun.