Scientists from the University of California San Diego, in collaboration with national and international institutions including Newcastle University, have identified how circadian clocks within microscopic bacteria precisely control gene expression over a 24-hour cycle.
The research, published in the journal Nature Structural and Molecular Biology, focused on cyanobacteria, also known as blue-green algae, and detailed the minimal components required for this regulatory system.
Core Clock Connections Revealed
The research team uncovered the connections between core components of cyanobacteria's 24-hour clock that regulate the rhythmic expression of genes.
Distinguished Professor Susan Golden, a senior author of the study, noted that a single signal from the clock can activate one set of genes while deactivating another. This process results in opposite phases of gene expression, where cellular processes peak at different times, such as dusk and dawn.
Study first author Mingxu Fang stated that only six proteins are necessary to reconstruct this clock and generate circadian gene transcription in cyanobacteria. Coauthor Kevin Corbett highlighted that this cyanobacterial clock system evolved independently from those found in humans and other eukaryotic organisms, indicating a distinct evolutionary pathway.
Methodology and System Development
Advanced cryo-electron microscopy, conducted at UC San Diego's Goeddel Family Technology Sandbox, was utilized in the research. Through this method, the team identified the core operating mechanisms of the clock.
With this understanding, researchers were able to build a clock that times transcription using purified components. They developed a synthetic gene expression system capable of rhythmically activating a test gene with a predictable expression phase. This system potentially has the capacity to be portable to other bacteria, such as Escherichia coli.
Potential Applications and Broader Context
Professor Yulia Yuzenkova from Newcastle University commented on the simplicity of the identified clocking mechanism and its ability to orchestrate complex cellular gene activity into rhythmic patterns.
The findings contribute significantly to the understanding of biological rhythms and have potential applications in various fields. These include microbial biotechnology, where such tools could be used to control the synthesis of specific biological products, and advancements in understanding human gut health.
The broader field of circadian biology is recognized for its relevance to health and medicine, influencing the timing of medications and vaccinations. UC San Diego recently established the Stuart and Barbara L. Brody Endowed Chair in Circadian Biology and Medicine to further research in this area.