Melvin Calvin Seminar Lecture in Organic Chemistry

Non-covalent interactions between biomolecules such as proteins and nucleic acids coordinate all cellular processes through changes in proximity. Tools that perturb, control, or reprogram these interactions have and will continue to be highly valuable for basic and translational scientific endeavors. Evolution, nature’s design philosophy, is not only a powerful method for optimizing molecular function but can also lead to the de novo discovery of novel mechanisms of activity of molecules. However, focusing Darwinian evolution on specific functions of molecules of interest is challenging. Here, I will present our groups work toward developing continuous in vivo evolution platforms to solve complex biophysical puzzles dealing with biomolecular interactions. I will describe our group’s proximity-dependent split RNAP biosensing technology, which when combined with Phage-Assisted Continuous Evolution (PACE), allows us to perform deep-mutational scanning experiments of biomolecular interfaces, to reprogram the specificity between biomolecular interfaces using evolution, to evolve “molecular glues” that drive biomolecular interactions, to evolve biocatalysts, and finally, to evolve selective inhibitors of target biomolecular interactions. Collectively, our work highlights how advances in synthetic biology can lead to novel functional molecules that provide solutions to challenges in biotechnology and medicine.

Speaker: Bryan Dickinson, University of Chicago