Investigating Cyanobacteria’s Many Paths to Adaptation

A new approach accelerates how quickly scientists can identify genes involved in environmental acclimation and understand bacterial stress.

Biological and Environmental Research

September 2, 2025

A guide RNA strand, in purple, guides CRISPR to a DNA strand. Scientists devised a method to identify genes that can be suppressed to customize microbes for biotechnology applications.

Image courtesy of Michelle Lehman/ORNL.

The Science

Cyanobacteria are the most abundant photosynthetic microorganisms on Earth. They live in nearly every habitat throughout the world, from permafrost to hot springs and from soils to oceans. Their ability to quickly acclimate and adjust to changing conditions is a long-standing area of research. However, the mechanisms that allow cyanobacteria to adapt to environmental fluctuations are very complex and poorly understood. Researchers have now applied a high-throughput method to cyanobacteria that toggles the expression of every gene in their genomes. It is helping scientists gain new insights into genes where minor transcriptional adjustments could allow cyanobacteria to flourish under varied light and temperature conditions.

The Impact

Cyanobacteria have valuable biotechnological applications. They are also important model organisms for basic research on photosynthesis. Gaining deeper insight into how they acclimate to extreme and fluctuating environments may reveal new opportunities for engineering more resilient biological systems. Furthermore, scientists can extend this gene editing approach to other microorganisms. Applying this approach will streamline the discovery of gene functions. This method can facilitate the development of microbes capable of producing valuable fuels, chemicals, and materials.

Summary

Cyanobacteria are the oldest photosynthetic organisms. They serve a significant ecological role across the planet. Their ability to survive in extreme conditions and quickly adjust to and survive in changing environments could provide key design principles towards understanding and engineering more robust plants and microbes. A team deployed a high-density, genome-wide CRISPR interference (CRISPRi) screen to identify subtle modifications in gene expression that improve growth of the cyanobacterium Synechococcus. The method was tested under environmental extremes such as changing light and/or temperature. This research uncovered both known and unknown targets for further study to better understand the dynamics of acclimation. The CRISPRi approach enabled a range of transcriptional adjustments to every gene in the Synechococcus genome. In this way, the researchers obtained a high-resolution view of gene function that would be difficult to obtain by simply turning genes on or off. This method offers more refined insights than traditional genome editing in cyanobacteria and other microbial systems.

Contact

Carrie Eckert, Ph.D.
Biosciences Division
Oak Ridge National Laboratory
eckertca@ornl.gov

Jerome Fox, Ph.D.
Chemical And Biological Engineering
University of Colorado, Boulder
jerome.fox@colorado.edu

Funding

This work was supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research Program and the United States Army Research Office. DNA synthesis was conducted by the DOE Joint Genome Institute, an Office of Science user facility.

Publications

Hren et al., High-density CRISPRi screens reveal diverse routes to improved acclimation in cyanobacteria. Proc. Natl. Acad. Sci. U.S.A. 122 (12) e2412625122 (2025). [DOI: 10.1073/pnas.2412625122]