Our internal clocks, known as circadian rhythms, are fundamental to health, orchestrating a vast array of biological processes over a 24-hour cycle. Disruptions to these rhythms – from jet lag to the seasonal shift of daylight saving time – can throw our bodies out of sync. But a growing body of research is revealing the intricate mechanisms behind these clocks, and a recent breakthrough at UC Merced is shedding new light on how these rhythms operate at the most fundamental level.
Researchers, led by biochemistry Professor Andy LiWang at UC Merced, have made significant strides in understanding how circadian clocks control gene expression in cyanobacteria – tiny, ancient organisms that represent a crucial link in the evolutionary history of life on Earth. Their work, detailed in a new paper published in the journal Nature Structural and Molecular Biology, identifies the minimal elements needed to control circadian gene transcription, the first step in the process of gene expression.
“Circadian biology is often framed in terms of sleep, jet lag and human health, yet the same principles govern the lives of tiny photosynthetic bacteria,” explained Professor LiWang. “By reconstituting the clock with its transcriptional machinery in a test tube, One can see the design rules that allow biological clocks to generate an internal representation of time and use it to control metabolic processes in anticipation of sunrise and sunset.”
Cyanobacteria, also known as blue-green algae, are remarkably simple organisms, making them ideal for dissecting the core components of a circadian clock. The researchers pinpointed the connections between key elements within the cyanobacteria’s 24-hour clock that govern the rhythmic activation and deactivation of genes. This discovery reveals how a single signal from the clock can simultaneously turn on some genes while switching off others, creating opposing phases of gene expression.
“We were able to show how a single signal from the clock can turn one set of genes on and another set off, generating opposite phases of gene expression. In that cell, that means some cellular processes are peaking at dusk and others at dawn,” said UC San Diego biological sciences Distinguished Professor Susan Golden, senior author of the study.
The significance of this research extends far beyond the study of microscopic organisms. Circadian clocks are increasingly recognized as central players in human health and disease. The timing of medication administration, for example, is now understood to influence its effectiveness, with drugs and vaccinations often performing best when aligned with our natural circadian rhythms.
This latest work is particularly notable because the circadian clock in cyanobacteria differs from those found in humans and other more complex organisms, known as eukaryotes. By studying this simpler system, researchers can gain fundamental insights into the universal principles governing biological timekeeping. The team has not only deciphered the clock’s mechanisms but has also successfully reconstructed it using purified components in a laboratory setting.
the researchers developed a synthetic gene expression system that could potentially be adapted for use in other bacteria, including Escherichia coli (E. Coli), a workhorse of biotechnology. This system allows for the rhythmic activation of a test gene with a predictable timing, opening up possibilities for controlling the production of valuable biological products.
“These are practical biological tools that can be expanded to control the synthesis of desirable biological products in cyanobacteria or in other kinds of microbes used in biotechnology,” Professor Golden stated.
The implications of this research are broad. Understanding how circadian clocks control genes at the molecular level could lead to the development of innovative biological tools for a range of applications, from optimizing industrial processes to enhancing agricultural yields. The ability to precisely control gene expression based on time could revolutionize biotechnology, allowing for the targeted production of pharmaceuticals, biofuels, and other valuable compounds.
UC Merced’s commitment to research is evident in Professor LiWang’s affiliations with the Department of Chemistry and Biochemistry, the NSF-funded CREST Center for Cellular and Biomolecular Machines, and the Health Sciences Research Institute. The university, as a whole, is increasingly recognized for its groundbreaking research across a wide spectrum of disciplines, including climate change, artificial intelligence, and health sciences. As highlighted on the UC Merced Research website, the institution fosters interdisciplinary collaboration and provides students with opportunities to participate in cutting-edge research.
The research was supported by funding from the National Institute of General Medical Sciences of the National Institutes of Health and the Biotechnology and Biological Sciences Research Council, underscoring the importance of continued investment in basic scientific research to unlock the secrets of life and improve human health.
