Research interests
Research in the laboratory focuses on developing nanoscale tools to study biological systems. These tools include instrumentation based on proximity probes, such as electrochemical tunnelling microscopy and spectroscopy, that we apply to investigate electron transfer in individual redox proteins, and other biophysical and biochemical interactions. These studies are relevant to the development of biosensors and molecular electronics devices, and have led to the discovery of long-distance electrochemically gated electron transport between partner proteins of the respiratory and photosynthetic chains. Another set of nanotools that we are developing is based on engineered molecular actuators that can be switched with light, such as azobenzene, which can be chemically attached to biomolecules in order to remotely control their activity (photopharmacology). They include peptide inhibitors of protein-protein interactions, small molecule enzymatic inhibitors, and photoswitchable ligands of a diversity of other proteins. Among several applications, these compounds have enabled photoactivated chemotherapy, photocontrol of cellular signaling mediated by ion channels and G protein-coupled receptors, photocontrol of cardiac activity and locomotion, pupillary reflex, sensory restoration, and photocontrol of brain waves. Based on these tools, we have also developed two-photon pharmacology to manipulate and study the activity of neurons and glia in intact brain tissue with pharmacological selectivity and sub-cellular three-dimensional resolution.