Subcellular optogenetic control for dissecting dynamic signaling networks


Patrick O'Neill, PhD, Postdoctoral Researcher, Host: Deborah Fygenson
Washington University in St. Louis, School of Medicine

Date and Location

Wednesday October 01, 2014 11:00am
1601 Elings Hall


Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but an understanding of how they dynamically orchestrate polarized cell behaviors has been hampered by a lack of methods to exert spatial and temporal control over specific signaling molecules inside a living cell. We have developed optogenetic tools that act downstream of native G protein coupled receptors (GPCRs) and provide direct control over the activity of endogenous heterotrimeric G protein subunits. These optogenetic tools allowed us to create reversible gradients of intracellular signaling activity in immune cells. Migratory responses generated by this approach show that a gradient of active G protein subunits is sufficient to generate directed cell migration. They also provide the most direct test so far for a dynamic signaling network motif that has been proposed to unify the directional sensing and adaptation capabilities of eukaryotic migratory cells.

Host:  Deborah Fygenson