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Light can switch this azobenzene-modified version of the circadian clock regulator longdaysin between its active and inactive forms, allowing researchers to controllably shift cells’ circadian clocks by up to 4 h.
Most living things contain a circadian clock — a signaling system that keeps the cell's function tied to the periodicity of a 24-h cycle. Although scientists
have identified many elements that regulate the clock's function, much about circadian rhythms and how they
influence health and disease remains poorly understood.
Now, researchers have created a light-activated molecule that can reversibly shift the length of the clock's cycle in living cells and tissues. The tool provides a targeted, non-invasive way to study how the clock affects cellular physiology, says
Ben Feringa, a chemist at the University of Groningen who co-led the work.
The team made use of an azobenzene moiety, which is commonly used as a photoswitch and which changes conformation upon exposure to light. Light converts azobenzene from the trans isomer, which is thermally stable, to the cis isomer, which is not. The cis isomer gradually reverts to trans on its own or can be converted photochemically. "It's just a change in geometry," Feringa says. In past work, Feringa's lab built light switches into other molecules including antibiotics and antitumor compounds.
In the new work, the researchers added an azobenzene light switch to a molecule called longdaysin that chronobiologist Tsuyoshi Hirota at Nagoya University had created previously. Longdaysin slows down the clock by interfering with the action of a key regulator of two genetic feedback loops that control the circadian clock.
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