Vibrational Spectroscopy of Optogenetic Rhodopsins
This event is part of the Preliminary Oral Exam.
Examining Committee: Kenneth Rothschild, Shyamsunder Erramilli, Tulika Bose, Carter Cornwall, Claudio Rebbi
Abstract: Optogenetics is a new approach that allows researchers to control neuronal activity with light. It is currently being used by neuroscientists for a variety of decisive applications such as probing the role of individual neurons in the brain. It also offers potential treatments for a variety of neurological disorders such as Parkinson's disease. A first step is the genetic targeting and expression of light-sensitive proteins called microbial rhodopsin in the plasma membrane of neurons of interest. One class of such microbial rhodopsins found in green algae, called channelrhodopsin (ChRs), functions as light-activated cation channels. In the resting state, light absorption by ChRs allows passive flow of cations into the neuron, raising the membrane potential (depolarization) and thus triggering an action potential. Although ChRs are widely used in neuroscience, the molecular mechanism underlying their function is not fully understood. Such basic knowledge would facilitate bioengineering of ChRs’ properties such as the wavelength of absorption, kinetics, and cation selectivity for specific applications. This talk will first review the use of resonance Raman spectroscopy and FTIR-difference spectroscopy that helped elucidate the molecular mechanism of bacteriorhodopsin, a light-driven proton pump, at the level of individual amino acids and internal water molecules. The latest results will then be presented on channelrhodopsin-1 from Chlamydomonas augustae (CaChR1), a cold-adapted alga which exhibits some similarities with bacteriorhodopsin. The talk will end with an outline of future work on other optogenetic proteins such as the florescent voltage sensing archaerhodopsin-3 and its mutants.