Optogenetic and chemogenetic technologies for probing molecular and cellular interactions
Spatial compartmentation underlies all cellular signaling, but existing methods to study the subcellular organization of endogenous proteins and RNA - by imaging and biochemical fractionation for example - have important limitations. We developed an alternative approach, enzyme-catalyzed proximity labeling, for the high-resolution spatial mapping of subcellular proteomes and transcriptomes in living cells. I will describe the development of this approach, which includes enzyme directed evolution, and its application to some new mitochondrial biology.
In the second part of the talk, I will describe synthetic protease-based optogenetic circuits that convert transient molecular events into stable cellular signals. I will give an example of how these tools can be used to access and study specific neuronal subpopulations that are activated during particular animal behaviors.