Optogenetic Tools

Optogenetic Tools

The ability to control the biochemistry and behavior of cells and organisms with a flash of light has elicited widespread attention, especially in the area of neurological diseases. Switching on the activity of a specific protein in a specific place in the brain offers the means to correlate with the behavior of cells and organisms.

Is it possible to recapitulate the series of steps that result in neurodegeneration in a specific area of the brain or block those steps by merely exposing the tissue of interest to a few light flashes? These questions, and many others, are now being addressed in a field that is now known as optogenetics.

Although light-responsive ion channels have been derived from lower microorganisms, creating light-responsive analogs of endogenous mammalian proteins represents a challenging engineering design problem. Is it possible to devise an optogenetic protein engineering strategy that is so straightforward that biologists can serve as their own protein engineers?

In this regard, members in our group have developed a potentially general strategy that draws its inspiration from the 100-year-old Michaelis Menten equation. This approach has furnished a light-activatable cofilin, light-mediated cell motility, a light-activatable bax, light-mediated cell death, and a light-activatable protein kinase. These proteins, in addition to others currently under development, are representatives of a large family of proteins known to modulate mitochondrial behavior.

Several neurological diseases, such as Parkinson's, Huntington's, Alzheimer's, and Charcot-Marie-Tooth type 2A, display defects in mitochondrial dynamics, including fusion, fission, transport, and turnover. Recent studies have suggested that it may be possible to ameliorate specific disease phenotypes by altering mitochondrial dynamics. We are exploring this premise by examining the ability of the light-responsive proteins under study to modulate mitochondrial behavior in a light-dependent fashion.

Research Areas

Light Activated Drugs

Light has been used, in conjunction with light-responsive agents, to control the biochemistry of cells, manipulate the behavior of organisms, and treat diseases such as cancer. We have designed a host of light-responsive sensors, inhibitors...

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Cellular Cyborgs

A typical human brain contains a hundred trillion synapses, which is three orders of magnitude larger than the hundred billion galaxies in the observable universe. This complexity represents one of the many challenges...

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Multicolor Monitoring

More than 150,000 people will be diagnosed with a hematological malignancy, for example leukemia, this year, joining the greater than 1,000,000 people living in the United States with these diseases. Although there has been significant...

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Personalized Pharmacology

One of the most compelling issues in preclinical and clinical drug discovery is the ability to accurately monitor drug action and patient responsiveness. For example, the heterogeneity of breast cancers requires that we create a means by...

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