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A constant battle between prokaryotes and phages has shaped how CRISPR is controlled and regulated. Haridha Shivram from Jennifer Doudna’s lab is working to understand these mechanisms, and in a recent review, he describes how this knowledge might enable us to build a better genome-editing tool. 
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About half of all bacteria studied and 90% of archaea use CRISPR-Cas systems to defend themselves against phages. In addition, prokaryotes have developed multiple mechanisms to control the expression of the CRISPR-Cas gene so that the defense can be stopped or activated as needed. However, phages retaliate and attempt to counter the defense via a diverse set of anti-CRISPR proteins (Acrs) that inhibit CRISPR-Cas activity and thus help the phage to successfully attack bacteria. Acrs have been experimentally exploited to reduce off-target edition by reducing the time available for Cas nuclease activity and increase tissue-specific edition by controlling their presence in various tissues. Understanding mechanically how CRISPR is regulated could lead to the improvement of CRISPR as a genome editing tool. Haridha Shivram, post-doctoral fellow at the University of California at Berkeley, has the research objective to discover new regulators of CRISPR-Case systems. The most fascinating aspect for him is how the arms race between the host and its invasive mobile genetic elements can lead to unique molecular innovations that can both help boost immunity but also reveal their hidden vulnerabilities. These evolving strategies can help make the CRISPR toolbox even better.