​​Luminopsins (LMOs)

Luminopsins are fusion proteins of a light-emitting luciferase and a light-sensing optogenetic element (channelrhodopsin or pump). Upon application of the luciferase substrate, coelenterazine, the luciferase emits light which activates the nearby opsin. Depending on the biophysical properties of the opsin, the neuron expressing the LMO will be activated or silenced.
We are continuously improving LMOs and broadening the concept of bioluminescence-driven optogenetics. We are also applying our current constructs to address the questions they were designed to answer.

Luminopsins

Applications of LMOs

​We are interested in the relationship between neuronal activity and shaping of neuronal circuitry resulting in the spectrum of “normal” to “abnormal” behavior. To this end we study the effect of early postnatal neuronal  hyper-excitation or hyper-inhibition on adult behavior. These experiments utilize mice genetically engineered to conditionally express luminopsins in defined neuronal populations.

We are also testing if we can utilize experimenter-induced neuronal activity to intervene in the neurodegenerative decline of brain function. Here we study the effect of neuronal excitation on alleviating motor defects in Parkinson’s disease. In these experiments we transplant neuronal stem cells expressing luminopsins into the brain of a genetic mouse model of Parkinson’s disease.

Furthermore, we are exploring the potential therapeutic effects of experimentally manipulated neuronal activity in regenerating injured neuronal circuits. Specifically, we are assessing the effects of stimulating luminopsin expressing spinal cord neurons following spinal cord injury in a rat model. 

We are currently looking for stu​dent volunteers who would like to gain valuable laboratory experience and those who would like to complete an honors capstone project and are interested in our ongoing neuroscience research. Please contact Dr. Ute Hochgesc​hwender for more information at hochg1u@cmich.edu.

Support & Collaborations

Our work is highly collaborative. Part of these collaborations are supported by The BRAIN Initiative. http://www.braininitiative.org/

The Brain Initiative
 
“NeuroNex Neurotechnology Hub: Bioluminescence for optimal brain control and imaging”
Collaboration with Christopher Moore (Brown University, Providence RI), Diane
Lipscombe (Brown University, Providence RI) & Nathan Shaner (Scintillon Institute, San
Diego, CA)

“Employing subcellular calcium to control membrane voltage”
Collaboration with Diane Lipscombe (Brown University, Providence RI) & Christopher Moore (Brown University, Providence RI)

“BioLuminescent OptoGenetics (BL-OG): A Novel and Versatile Strategy for Neuromodulation”
Collaboration with Christopher Moore (Brown University, Providence RI) & Nathan Shaner (Scintillon Institute, San Diego, CA) 

“Bioluminescent Optogenetics to Autoregulate Excitable Cells”
Collaboration with Christopher Moore, Diane Lipscombe, Julie Kauer, Barry Connors (Brown University, Providence RI)