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New Type of Optogenetic Protein Can Also Be Controlled by Temperature

New Type of Optogenetic Protein Can Also Be Controlled by Temperature

New Type of Optogenetic Protein Can Also Be Controlled by Temperature

New Type of Optogenetic Protein Can Also Be Controlled by Temperature

The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. At higher temperatures, however, the proteins become rapidly inactivated and thus do not stay at the membrane, resulting in the duller edges seen in the bottom right panel. Credit: University of Pennsylvania
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Most organisms have proteins that react to light. Even creatures that don’t have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth and cell survival.

The field of optogenetics relies on such proteins to better understand and manipulate these processes. Using lasers and genetically engineered versions of these naturally occurring proteins, known as probes, researchers can precisely activate and deactivate a variety of cellular pathways, just like flipping a switch.

Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new horizons for both basic science and translational research.

Lukasz Bugaj, assistant professor in bioengineering, Bomyi Lim, assistant professor in chemical and biomolecular engineering, Brian Chow, associate professor in bioengineering, and graduate students William Benman in Bugaj’s lab, Hao Deng in Lim’s lab, and Erin Berlew and Ivan Kuznetsov in Chow’s lab, published their study in Nature Chemical Biology. Arndt Siekmann, associate professor of cell and developmental biology at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.

“Compared to previous probes, ours were based on a single protein called BcLOV4, which was recently described by Brian Chow’s lab,” says Bugaj. “As a single protein, BcLOV4 can stimulate signals in a manner that required multiple proteins in previous approaches, thus making it simpler and easier to use.”

The authors successfully showed that BcLOV4-based probes could stimulate the Ras and PI3K pathways in mammalian cells, as well as in zebrafish and fruit flies, two common model organisms.

“However, in the course of our experiments, we serendipitously discovered that BcLOV4 could sense not only light, but also temperature,” says Bugaj. “As far as we know, this type of dual light and temperature sensitivity is a completely new feature for photosensory proteins.”

Reference: Benman W, Berlew EE, Deng H, et al. Temperature-responsive optogenetic probes of cell signaling. Nat Chem Biol. 22, 2021:1-9. doi: 10.1038/s41589-021-00917-0

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