Bioluminescence is a naturally occurring phenomenon used by various animals to produce light. For example, the firefly uses this mechanism, as well as several deep-sea creatures. Capitalizing on biological systems to emit and received light, the investigator will design a system that can be used to treat neurological disorders. They propose to genetically engineer neural cells to express two unique proteins. The first set of proteins will emit photons (light) every time that they bind the neurotransmitter glutamate. The second set of proteins will receive the photon and harvest its energy to allow the entry of ions onto neurons. This new genetically encoded pair of proteins will enhance the communication between the neurons at site of lesion and potentially augment recovery after spinal cord injury.
Bioluminescent light is produced as a result of the catalytic interaction of a specialized enzyme (luciferase) and its specific substrate (luciferin) resulting in the production of photons. They are working to engineer these enzymes to develop BioLuminescent INdicators of Glutamate (BLING) for direct optical detection of the excitatory neurotransmitter glutamate. BLING will allow neuroscientists to study the central nervous system in behaving animal models in ways not previously possible. Next, they use BLING for neuromodulation as an approach to spinal cord injury rehabilitation. They will take advantage of existing light sensitive ion channels that can activate or inhibit neuronal activity in response to light. Since BLING generates light in a glutamate dependent manner, they will utilize BLING as the activation source for these light sensitive ion channels to control neuronal activity for glutamate dependent neuromodulation. The goal is to enhance neuronal connections by amplifying excitatory synaptic activity from the brain to the spinal cord below the level of injury to compensate for damage caused by injury. They anticipate this approach to be highly effective for the treatment of a variety of other neurodegenerative disorders.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
