Though much progress has been made both in identifying and inhibiting protein-protein interactions (PPIs), the field lacks platforms that can probe the basic biology of PPI selectivity and identify inhibitor candidates in an efficient, rapid manner. Continuous experimental evolution poses such a platform to address these needs due to the versatility of biosensors employed and the swift selection for desired properties. My first project in graduate school addressed the former area of study and was published in eLife. In this work, we developed a continuous evolution system by which to evolve, and therefore study, PPIs.<br/>By incorporating dual selection in Phage-Assisted Continuous Evolution (PACE), we constructed a method that can evolve specificity in PPIs rather than binding alone, which is a key aspect of how PPIs function in biology. By combining this method with ancestral sequence reconstruction, we performed parallel multi-replicate continuous experimental evolution campaigns, which achieved hundreds of rounds of evolution in days, to alter the binding specificities of two-phenotypically divergent yet genetically-related modern-day proteins and their predecessors. High-throughput sequencing and mutational reconstructions allowed us to assess the roles of chance and contingency in the evolution of this protein family and yield insights into the molecular basis of specificity.<br/>In current efforts, I am using the previous project to inform design on a platform to identify PPI inhibitors. Such a method would provide a great resource in an area of drug development that struggles with quickly identifying molecules with inhibitory potential and with attaining specificity.

Modulating protein-protein interactions through phage-assisted continuous evolution

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.