Grant: Operating Grant

Proteins are the tools that orchestrate and perform the countless biochemical reactions required for thought, growth, and proliferation. Proteins are also one of the most important classes of tools used for the study of these very same biochemical processes. For example, fluorescent proteins from marine organisms enable researchers to genetically target fluorescent probes to the nerve cells of a model organism and thus visualize neuronal dynamics in whole animals. However, while structure is important, neuroscientists are much more interested in visualizing neuronal function. We propose to use protein engineering to create the next generation of imaging tools which will make the visualization of neuronal function a widely accessible experimental reality. Protein engineering is an endeavour that is focused on improving the properties of proteins and rendering them more useful for practical applications. To achieve the goals of this grant we propose to focus our protein engineering efforts on specific classes of proteins: fluorescent protein-based biosensors of intracellular messengers, and rhodopsin-based biosensors of membrane potential. Using powerful protein engineering and directed protein evolution strategies, we will modify and optimize these biosensors for improved performance in functional neural imaging. The resulting biosensors will be validated in model systems and initially applied to studies of central nervous system development and synaptic transmission. Ultimately, these new probe molecules will provide the neuroscience community with new windows into the transmission of signals through neural networks, and will lead to an improved understanding of the fundamental processes underlying brain function and disease.