When it comes to bridging gulfs, Ed Tate believes that the gap between chemists and biologists can require the greatest leap to overcome. “Engineers and physicists tend to treat biology as a technical problem to solve,” he says, “whereas translating biology into the language of chemistry brings both new opportunities and different challenges.”
Instead of focusing primarily on genes, as biologists do, chemists are most interested in molecular interactions. Ed jokes that a traditional chemist’s motivation is “can I get my molecules to do something that yours can’t?” But becoming bilingual in chemistry and biology or finding a collaborator who can act as your own personalized Google Translator can be immensely rewarding, both intellectually and practically.
Ed points out that whilst our 20,000 or so protein-coding genes are responsible for genetic diversity, the complexity of the protein universe within our cells is far larger. For example, post-translational modification, the process whereby other molecules are added on to the bare bones of a protein, means that those 20,000 unique genes can make millions of distinct proteins. Figuring out what those post-translational modifications do—and what changes in the interactions modified proteins can make—is an important part of the basis of biological regulation, and hence of life.
Overcoming the challenges of doing chemistry in a messy living cell with its annoyingly watery contents that make clean, specific reactions very difficult, lies at the heart of chemical biology. Ed’s specialty is investigating lipidation or “the addition of grease to proteins,” as he puts it. Over the years, his lab has developed a broad range of chemical probes able to bind selectively to the different types of lipid that decorate proteins. When introduced into cells, these molecular spies can be used to track the lipidated proteins, documenting when, where and with whom they interact. The lab has also collaborated with structural biologists to design inhibitory compounds that prevent specific enzymes from lipidating their targets.
This is not just an interesting exercise in chemical espionage; in its role as a molecular address label and arbiter of protein association, lipidation is of fundamental importance to pretty much everything that a cell does. And in cancer, it’s been shown that changes in lipidation are associated with development and progression of the disease.
Despite the importance of dysregulation of protein lipidation in cancer, the full scope and extent of the changes aren’t clear, largely due to the difficulties of looking at lipidation on a
cell-wide scale. Ed’s lab is perfectly positioned to remedy this, a recent programme grant from Cancer Research UK enables him and his collaborators to define the roles of protein lipidation in the life and death of a cancer cell. Their aim is to provide the first quantitative, system-level view of protein lipidation in aggressive and drug-resistant cancers, with the hope of finding clinically useful ways of targeting lipidation mechanisms.
In a world where ‘pure’ chemistry is becoming harder to fund, Ed encourages his fellow chemists to branch out, and take a look at what biology has to offer: “Chemical insight is hugely in demand and somewhere out there is a biologist who has a question you’ll enjoy answering together!”