Revolutionizing Biosensor Engineering Using Plant Hormone Receptors with Dr. Whitehead

The ability to engineer biosensors for user-specified molecules could significantly advance numerous biological applications. In this episode, we have the privilege of hosting Dr. Whitehead, who has made strides towards a method for rapidly engineering such biosensors. The team used PYR1, a plant abscisic acid (ABA) receptor known for its adaptable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which aids in constructing sense-response functions. The researchers successfully evolved 21 sensors with sensitivities ranging from nanomolar to micromolar for various small molecules, including structurally diverse natural and synthetic cannabinoids and multiple organophosphates. Through X-ray crystallography analysis, they revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. Furthermore, the team demonstrated that the PYR1-derived receptors could be effectively ported to various ligand-responsive outputs, including ELISA-like assays, luminescence by protein-fragment complementation, and transcriptional circuits, all with picomolar to nanomolar sensitivity. Join us as we dive into Dr. Whitehead's fascinating work with the PYR1 scaffold and how it could revolutionize the creation of new biosensors for a broad spectrum of sense-response applications.Keywords: Biosensors, Engineering, Dr. Whitehead, PYR1, Abscisic Acid, Cannabinoids, Organophosphates, Ligand-responsive Outputs, ELISA, Protein-fragment Complementation, Transcriptional Circuits.Beltrán, J., Steiner, P.J., Bedewitz, M. et al. Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-022-01364-5