Research

Optogenetic control of GPCR and G protein signaling

In order to understand GPCR signaling dynamics with subcellular detail, we have developed several tools for optogenetic control of GPCRs and G protein subunits. Our early work focused on using these tools to dissect the intracellular signaling networks that control polarization and directional migration of immune cells. We currently focus on leveraging optical control of GPCR signaling to generate new tools for studying neural circuit functions. For example, we recently collaborated with Bryan Copits (Washington University in St. Louis) and Michael Bruchas (University of Washington), to develop a bistable, photoswitchable GPCR for optically controlled inhibition of neurotransmission at axon terminals. We are currently collaborating with the Copits Lab to develop next generation GPCR-based optogenetic tools with synapse-subtype specificity.

Neuroanatomical imaging of GPCR signaling

We are developing a new approach for in situ imaging of G protein activation by GPCRs in brain tissue sections. The goal is to quantify, with subcellular resolution and neuroanatomical detail, GPCR activation of the different G protein subtypes. The long term goal is to use this approach to identify specific changes in GPCR signaling that occur in response to chronic drug use, chronic stress, or chronic pain, to help identify pharmacological targets for new therapies.