Infectious Disease & Microbiome Program, Chemical Biology & Therapeutic Sciences Program, Broad Institute
The development and application of methods for the laboratory evolution of biomolecules has rapidly progressed over the last few decades. Advancements in continuous microbe culturing and selection design have facilitated the development of new technologies that enable the continuous directed evolution of proteins and nucleic acids. These technologies have the potential to support the extremely rapid evolution of biomolecules with tailor-made functional properties. Continuous evolution methods must support all of the key steps of laboratory evolution — translation of genes into gene products, selection or screening, replication of genes encoding the most fit gene products, and mutation of surviving genes — in a self-sustaining manner that requires little or no researcher intervention. In this presentation, I will describe the basis and applications of our Phage-Assisted Continuous Evolution (PACE) platform, focusing on the impact of mutagenesis efficiency and selection stringency modulation during directed evolution campaigns. Through these tools, we aspire to enable researchers to address increasingly complex biological questions and to access biomolecules with novel or even unprecedented properties.