Dec 4, 2024

Davidson Lab: Discovery and Characterization of AcrIF25: Novel Anti-CRISPR Protein

By MoGen Communications

Scientists in Davidson Lab Discovers a New Anti-CRISPR Protein

Researchers at the University of Toronto’s Department of Molecular Genetics have uncovered a new anti-CRISPR protein, AcrIF25, that inhibits CRISPR-Cas systems by dismantling a key molecular complex in bacteria.

The study, led by first author and post-doctoral researcher Chantal N. Trost, with Dr. Alan Davidson as the corresponding author, was recently published in the prestigious scientific journal Nature. It describes how AcrIF25 targets the type I-F CRISPR-Cas system in Pseudomonas aeruginosa, a bacteria that is a common cause of infections, particularly in patients with weakened immune systems.

In the study, the team demonstrated that AcrIF25 blocks CRISPR-Cas activity by disassembling the Csy complex, which is essential for the system’s DNA-targeting function. AcrIF25 works in a completely novel way, disrupting the CRISPR-Cas system by pulling apart the components of the complex one by one without the use of an external energy source like ATP.

Using techniques such as X-ray crystallography and fluorescence spectroscopy, the team showed that AcrIF25 specifically targets the Cas7 subunits of the Csy complex, starting with the most accessible one. This discovery adds to the growing body of research on anti-CRISPR proteins, which are potential tools for controlling CRISPR-based genome editing.

The researchers are now exploring how AcrIF25 and other anti-CRISPR proteins can be harnessed for applications in biotechnology and medicine, such as improving the precision of CRISPR-based therapies.

This discovery not only enhances our understanding of CRISPR-Cas inhibition but also opens new possibilities for biotechnological applications. AcrIF25 could be harnessed to:

  • Develop novel tools for controlling CRISPR-Cas activity
  • Create new strategies for RNA delivery into cells
  • Combat antibiotic-resistant bacteria

This research was supported by the Canadian Institutes of Health Research (CIHR) Post-Doctoral Fellowship Award, the Natural Sciences and Engineering Research Council of Canada (NSERC), the Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Academy of Sciences, and the Beijing Municipal Science & Technology Commission.