Our research
We use directed evolution, cellular engineering, and high-throughput robotics to expand the druggable space of genetically and epigenetically mis-regulated diseases.
We use directed evolution, cellular engineering, and high-throughput robotics to expand the druggable space of genetically and epigenetically mis-regulated diseases.
We use directed evolution, cellular engineering, and robotics to expand the "druggable" space of genetically and epigenetically mis-regulated diseases.
Within synthetic biology, there is enormous potential to converge the seemingly discrete fields of molecular evolution, epigenetics, and cancer. However, methods to combine these fields are limited by the inability to assess the complexities of protein evolution, population heterogeneity, and gene regulation simultaneously. The Chory lab combines directed evolution, epigenome engineering, and robotics to engineer new proteins, biological tools, and cellular therapies with both translational and basic science potential.
Automated liquid handling and feedback control let us run hundreds of experiments in parallel.
Mutation, selection, and replication recreated in the lab so useful variants enrich on their own.
Engineering mammalian systems, delivery, and the genetic circuits that control them.
Following variants across generations to see which changes survive selection and why.
Directed evolution is recreating the processes of mutation, selection, and replication in the lab. We use directed evolution to create new proteins with therapeutic value, and to study how evolution gives rise to phenotypes that confer human diseases.
We use phage-based evolution to engineer new proteins. Coupled with novel automation platforms, we can rapidly evolve proteins with PRANCE, and use open-source automation (PyHamilton) to engineer new cellular therapies.
Phage-Assisted Continuous Evolution. Bacteriophage continuously evolve proteins and genetic elements in bacteria, with function tied to replication.
Esvelt, Carlson & Liu, Nature 2011
Phage- and Robotics-Assisted Near-Continuous Evolution. Adds robotics and feedback control to run hundreds of evolution experiments in parallel.
DeBenedictis, Chory et al., Nature Methods 2022
Evolves proteins against several objectives at once, with many turbidostats holding cells at constant density for tight control of selection at scale.
Read the paper
Parallel automated bioreactors hold cells at constant density for tightly controlled growth and selection, independent of phage. The same platform will extend to our mammalian and VACE systems.
Chory et al., Molecular Systems Biology 2021
Disease is an evolutionary problem. A cell acquires a mutation, gains a Darwinian fitness advantage over its neighbors, and outcompetes them. The same logic that lets a tumor escape treatment, or a pathogen escape a drug, is the logic we turn back on itself: we run evolution deliberately, under controlled selection, to build the proteins and tools that can keep up.
That approach spans therapeutic discovery, chromatin and gene regulation, and the automation needed to explore sequence space at scale.
If you're interested in any of the following projects, we would love to have you join us.
Commercial liquid handlers cost more than most labs can justify, which puts high-throughput biology out of reach. We are building an open-source liquid handler: a fully documented, low-cost instrument that runs the same protocol code as commercial machines through PyLabRobot. We also build and maintain the open-source software that drives it, and contribute to PyHamilton and PyLabRobot, so that high-throughput biology is reproducible and accessible to any lab. Parts list, firmware, and code are all open.
Open-source resourcesVideo credit: Alexandra Sanchez
Our work is supported by federal agencies, foundations, and individual gifts. Gifts to the lab go to trainee support, reagents, and the open-source hardware we release for any lab to use.