The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. The duller edges of the bottom right panel are caused by the rapid inactivation of the proteins at higher temperatures. The University of Pennsylvania.
Most organisms have light-sensitive genes. Many cellular processes, such as transcription, translation, cell growth and cell survival, are regulated by these proteins by creatures that don't have eyes or other visual organs.
The field of optogenetics depends on such proteins to understand and manipulate these processes. Using lasers and genetically engineered versions of naturally occurring proteins, known as probes, researchers can precisely activated and deactivated a variety of cellular pathways.
Penn Engineering researchers have described a new type of optogenetics that can be controlled by both light and temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new doors for research.
graduate students William Benman in Bugaj's lab, Brian Chow in the lab of the assistant professor, and Hao Deng in the lab of the assistant professor. The Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine and a research technician in his lab contributed to this research.
The team wanted to develop a single component probe that would be able to manipulate specific cellular pathways more efficiently. The model for their probe was a protein called BcLOV4 and through further investigation of its function, they discovered that it is controlled by both light and temperature.
Bugaj says that light-activated proteins are a new kind of research tool that have increased the precision in how we study and understand cell function. Our original goal was to create simpler, more effective tools to control two separate signaling pathways that are central to cell biology and are implicated in cancer.
Understanding the role of the cellular signaling pathways, Ras and PI3K, may help us understand how healthy cells react to disease and why tumors grow and spread.
Traditional probes for these pathways typically involve two separate optogenetics that need to be adjusted in a cell. It is more difficult to look at tissues or entire organisms when looking at individual cells.
Bugaj says that their probe was based on a singleprotein called BcLOV4 which was recently described by Brian Chow's lab. BcLOV4 can be used in a simpler and easier way than previous approaches because it is a single protein.
The authors showed that BcLOV4-based probes could be used to induce the pathways in mammals.
Bugaj says that BcLOV4 could sense both light and temperature. This type of dual light and temperature sensitivity is a completely new feature for photosensory proteins.
The majority of our paper describes the dual light and temperature sensitivity, explores different experimental systems beyond mammals, and describes new experimental capabilities that leverage light and temperature sensitivity.
The team modeled various light and temperature conditions to predict how the optogenetic protein would respond. They found that they could control multiple light-sensitive proteins in the same cell by using temperature.
Bugaj says that their work shows an example of a photosensory proteins that responds to light and temperature, and implies that other such proteins may exist. New possibilities for more sophisticated, multi-input remote control of cell function have been opened by this discovery. Our work has implications for the new field of thermogenetics, which is already being used as a remote control of engineered cell therapies in animal models.
He says that the temperature-sensitive behavior of BcLOV4 is unlike any that has been described before. The promise of a completely new class of temperature-responsive proteins with unique capabilities is held by theProtein that changes subcellular localization based on temperature.
William Benman and his team have a paper on Temperature-Responsive optogenetic probes of cell signaling. There is a DOI of 10.1038/s41589-021-00917-0.
Nature Chemical Biology has a journal.
Light and temperature can control the function of the cell signal pathways.
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