Ryan Rezvani Rose Hills
The Directed Evolution of Novel G-Protein Coupled Receptors for Orthogonal Binding with Select Ligands
G-Protein coupled receptors (GPCRs for short) are a class of membrane proteins that bind to a specific chemical stimulus, an interaction which then initiates a cellular response pathway. Such a mechanism is present in most eukaryotic organisms, where it governs over processes like olfactory responses, neurochemical signal reception from chemical compounds, or the systematic release of hormones. The manipulation of GPCR-mediated pathways can allow for novel cellular responses to a ligand of choice, a phenomenon that can be expanded to the scale of a whole nervous system if implemented uniformly into an organism. Such a level of functional control necessitates the mutagenesis of the GPCR with a selection pressure in place that drives the evolution of the protein towards a specific end goal. I intend to the extend the boundaries of GPCR evolution through the introduction of more robust mutagenesis and novel combinatorial library designs, allowing for greater protein variation.