BroadCASTing DNA in bacteria: Mechanisms of CRISPR-associated transposons

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• Irma Querques
• Tuesday 25 February 2025, 12:00-13:00
• Jean Thomas Lecture theatre, Sanger Building, Tennis Court Road.

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CRISPR -associated transposons (CASTs) are a unique class of bacterial mobile genetic elements that combine the mobility of transposons with the precision of CRISPR -Cas systems, enabling RNA -guided DNA insertion at specific genomic sites. This property holds great promise for applications in genome editing. Our research focused on type V CAS Ts, which rely on the pseudonuclease Cas12k, the transposase TnsB, the zinc-finger protein TniQ, and the ATPase TnsC to facilitate targeted DNA integration. By employing an integrative structural and biochemical approach, we have characterized the key molecular interactions within the CRISPR -Cas12k complex and the TnsC protein filament. Our findings reveal how the arrangement of guide RNAs and the assembly of TnsC filaments induce structural changes in DNA , offering mechanistic insights into the RNA -guided DNA targeting process. In our most recent work, we discovered an unexpected interaction between the CRISPR machinery and the ribosomal protein S15 , unveiling a novel regulatory role for S15 that goes beyond its traditional function in ribosome assembly. This discovery adds an additional layer of control over transposon activity and has important implications for harnessing CAS Ts as programmable tools for gene insertion. In this talk, I will share our findings on the structural basis of RNA -mediated DNA transposition and discuss the broader implications of CAS Ts in natural horizontal gene transfer and their potential applications in biotechnology.

This talk is part of the Department of Biochemistry - Tea Club Seminars series.

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• Cambridge Infectious Diseases
• Department of Biochemistry - Tea Club Seminars
• Jean Thomas Lecture theatre, Sanger Building, Tennis Court Road
• PMRFPS's
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