Our laboratory creates new, genetically encoded fluorescent
biosensors to solve fundamental problems in neuroscience.
We currently have two research goals in the laboratory that address fundamental problems in neurobiology.
Fluorescent biosensors for optically recording from excitable cells.
Advances in electronics and neurobiology have made it possible record from excitable cells such as the neurons of the brain. It is now common place for the neuroscientist to record from a neuron and to understand when it responds in relation to a particular stimulus or before a movement. This has produced tremendous advances in neuroscience, in our understanding of the brain, but we are only listening to one, or a few, neurons at a time. Even simple nervous systems involve hundreds of cells and thousands of connections, and we need to understand how the entire circuit works. One way of doing this involves electrically recording from many different neurons at the same time. Our colleague Charles Gray is pioneering new ways of recording from many neurons at the same time. In our lab we are trying to create new generations of genetically encoded fluorescent proteins that will signal voltage changes when a neuron fires. This is work that we are doing with our collaborator, Ehud Isacoff at UC Berkeley. Put simply, we are trying to fuse jellyfish fluorescent proteins to voltage-gated ion channels to produce a biosensor that we can then express in the nervous system so that neuroscientists can optically record the activity of entire neural networks.
Looking at intracellular signaling
There are many signaling pathways in cells beyond simple changes in voltage. Proteins talk with one another to regulate excitability, gene expression, and even the decision of whether to live or die. We are currently developing new fluorescent methods for watching these protein interactions in real time and in living cells. This work involves fusing two different fluorescent proteins to a signaling protein such that we create a FRET based biosensor. This sort of work is producing new ways of measuring intracellular signaling, and it is our hope that some of the biosensors will speed up the process of searching for new, important drugs.