SAN FRANCISCO, Sept. 19 (Xinhua) -- Protein engineers and neurobiologists at the University of California, San Francisco, or UCSF, have teamed up to create a biological "light saber," an engineered protein that can slay specific cells simply by exposing them to light.
The work, published in the National Academy of Sciences (PNAS), addresses the reality that while the ability to selectively eradicate specific types of cells from multicellular organisms allows scientists to decipher those cells' functions, the surgical, chemical or genetic tools to do so are imprecise and far from ideal.
Such cell ablation techniques have been particularly important in neuroscience. Some of the earliest insights on brain function were based on observations of patients who had specific lesions in different brain areas.
The new study reports that the protein uses light to leverage apoptosis, a natural "cell-suicide" pathway by which cells can trigger their own death under certain circumstances. The protein is dubbed "Caspase-LOV," so called because it links LOV (light-oxygen-voltage-sensing domain), a molecular light sensor derived from oats, to caspase-3, the human version of an enzyme that is crucial to apoptosis.
Because apoptosis is a fundamental biological process, employed during normal development to prune unneeded cells, and to dispose of defective ones, it is razor-sharp and induces a clean, non-inflammatory form of cell death. When cells are acutely injured, they spill all their contents, but apoptotic cells shrink and are absorbed by neighboring cells or by immune cells, so the caspase endgame is a tidy cell death without any inflammation of surrounding tissue.
"Caspases are like demolition experts," James A. Wells, professor of pharmaceutical chemistry at the UCSF School of Pharmacy, and co-senior author of the study, noted in a news release from UCSF. Other researchers on the project included graduate student Ashley Smart and Graeme "Grae" Davis, the Albert Bowers Professor and chair of the Department of Biochemistry and Biophysics at UCSF.
Since light easily penetrates the embryos of the fruit fly Drosophila, the authors believe Caspase-LOV will be immediately useful to labs that study this model organism, and it could eventually be used in other organisms, such as mice, by using fiber optics to illuminate and precisely eliminate cells.
The team demonstrated in their study that when the Caspase-LOV was expressed in fruit-fly motor neurons, those neurons died upon exposure to light, thus affecting the flies' ability to move. Similarly, the team was able to selectively ablate specific cells in the retina simply by exposing the fruit fly's compound eyes to light.
As the duration of light exposure is directly correlated with the extent of cell death, Wells was quoted as explaining, Caspase-LOV could be a powerful tool to explore the mechanisms of neurodegeneration, a process that occurs over an extended period of time in human diseases such as Alzheimer's and Parkinson's.
