Researchers at the University of California San Diego have made significant progress in understanding the mechanisms of circadian clocks in microscopic organisms. Their findings, published in the journal Nature Structural and Molecular Biology, shed light on how circadian clocks in cyanobacteria—tiny aquatic organisms also known as blue-green algae—regulate gene expression in a 24-hour cycle.
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The study, conducted by scientists from UC San Diego’s Department of Molecular Biology and Center for Circadian Biology, along with collaborators from Newcastle University in the UK, revealed how a single clock signal controls the timing of various genes, resulting in different cellular processes peaking at dusk and dawn. Senior author Susan Golden, a Distinguished Professor of Biological Sciences, explained that the research demonstrates how specific gene sets are turned on and off at different times of the day.
The importance of circadian biology has been underscored by its implications in health and medicine, as the timing of medications and vaccinations can enhance their effectiveness. In recognition of this area of research, UC San Diego established the Stuart and Barbara L. Brody Endowed Chair in Circadian Biology and Medicine, appointing Amir Zarrinpar to this inaugural position.
The researchers identified the essential components needed to reconstruct the circadian gene transcription system in cyanobacteria. Mingxu Fang, the first author of the study and a former postdoctoral scholar at UC San Diego, noted that just six proteins are needed to replicate this clock mechanism. This discovery distinguishes the bacterial clock from those found in humans and other eukaryotes, as it evolved independently, according to coauthor Kevin Corbett.
The team utilized cryo-electron microscopy to visualize these core components, allowing them to build a functional clock that regulates gene expression. They successfully created a synthetic system capable of rhythmically activating a test gene, indicating potential applications for managing gene synthesis in microbial biotechnology.
Yulia Yuzenkova, another coauthor from Newcastle University, highlighted the elegance of how a simple clock mechanism can create rhythmic patterns of cellular activity. The research not only advances understanding of biological rhythms but also has implications for areas ranging from biotechnology to human health.
The study's coauthors include Yajie Gu, Miron Leanca, Mariusz Matyszewski, and Andy LiWang. Funding was provided by the National Institute of General Medical Sciences of the National Institutes of Health and the Biotechnology and Biological Sciences Research Council.