Development of a voltage sensitive fluorescent protein / Organization of the mammalian odorant and pheromone detection systems

The brain is an electric organ. Therefore, being able to monitor membrane voltage of neurons is crucial for understanding of how the brain works. While it is possible to monitor electrical activity of neurons both directly (using electrodes) and indirectly (using voltage sensitive dyes), both of these approaches have severe limitations. Electrophysiological methods allow monitoring of only a few cells at a time. Voltage sensitive dyes have seen only limited applications due to their toxicity and low staining selectivity. Having a genetically encoded optical sensor of membrane voltage, a voltage sensitive fluorescent protein, would avoid the drawbacks of the current methods and allow detailed monitoring of complete neural circuits and neuronal assemblies. This in turn would allow us to decipher the organizing principles of the brain, as well as the particulars of individual neural systems. Our goal is to understand how the brain works. That is why we are working on developing a voltage sensitive fluorescent protein.

Developing a usable voltage sensitive fluorescent protein is a hard, multidisciplinary problem. While several attempts to solve it have been published by laboratories at top universities, no one has so far succeeded. Using innovative approaches spanning methods of non-linear optics, mathematical modeling, biophysics and molecular biology, we have made significant progress, and we are expecting several major papers to come out of our lab in near future.

Along the way towards developing a voltage sensitive fluorescent protein we have gained insights that should allow rapid development of genetically encoded sensors of many cell processes, with numerous scientific and commercial applications. Thus, while maintaining focus on development of a voltage sensitive fluorescent protein, we are now developing other genetically encoded sensors as well.

Of particular interest to us are sensors of various aspects of neural activity (activation/inactivation of receptor proteins, opening/closing of ion channels), especially if applicable to studies of mammalian olfactory/pheromone detection systems. While our past work focused on biochemistry of soluble proteins involved in odorant/pheromone transport and recognition, our current interest lies in the development and organization of the neural systems responsible for detection and recognition of odorants and pheromones in mammals.