Emma Chory Uses Robotics to Speed Up Cellular Evolution

Emma Chory will join Duke University's Department of Biomedical Engineering, beginning July 1, 2023. By adapting commercial automated robotic platforms to rapidly engineer targeted proteins and biomolecules, Chory aims to explore how researchers can use evolution to create compounds with therapeutic value and study mutations that cause diseases like cancer.

Chory specializes in a process known as directed evolution. This method mimics the process of natural selection that occurs in nature, where an environmental pressure, like warm temperatures or the need to blend in with leaves, will cause an organism to adapt and change. If these changes are positive, then the organism will be more robust, and these changes will be inherited by their progeny.

In directed evolution, researchers can engineer proteins or different molecules to evolve to gain key characteristics, like the ability to inhibit cancer cell growth. This is achieved by changing a gene's DNA, selecting promising variants from that mutation, and replicating those variants.

"Directed evolution is recreating the natural process of mutation, selection and replication, but doing it in a lab, where we can accelerate evolution to improve biomolecules toward a specific characteristic or function," explains Chory. "By doing this on a large scale, we can generate a lot of data all at once about why certain molecules may gain or lose function, and from there we can investigate the conditions and mutations that led to that change."

But this scale is difficult to achieve in an academic lab. After all, it's not possible for graduate students and laboratory staff to perfectly grow, mutate, select and replicate target genes across more than 400 different cell lines every 12 hours.

Instead, Chory turned to the robotic platforms usually reserved for pharmaceutical companies. These tools, roughly the size of a lab bench and commercially available, are often used to automate jobs like pipetting, or to create therapeutics--like covid vaccines--on a mass scale. But Chory and her team developed their own software, called Pyhamilton, that enables these machines to be used for directed evolution experiments.

As a post-doctoral fellow at MIT, Chory and her team built on this work to develop the platform PRANCE, or phage-and robotics-assisted near-continuous evolution. The adaption of PRANCE has enabled Chory to run her experiments at impressive scales, giving her the opportunity to explore how population diversity, the timing of environmental changes, and even random mutations can affect how bacterial proteins evolve.

Chory will continue this work at Duke, where her lab will turn their attention toward cancer.

"Because we'll be working with large amounts of data about how and why a protein evolves, we'll be able to answer more basic science questions that we haven't been able to uncover before. This will help us better understand the underlying disease mechanisms," she says. "But we'll also be able to use this process to help promising proteins and biomolecules evolve in a way that could make them ideally suited to combat different types of cancer. There are a lot of opportunities."

With a PhD from Stanford, where Chory's work spanned cancer biology, epigenetics and stem cell engineering, and robotics experience from MIT, Chory's unique background has made her appreciate collaborative research environments, which is one of the reason's she's excited to join Duke BME.

"Having the opportunity to be in a department that is very close with both its medical school and a premiere genomics center like Duke's Center for Advanced Genomic Technologies is a very rare combination," says Chory. "I don't think there are many programs in the world like that, and I'm excited to get my own collaborations started."

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