Multistable and dynamic CRISPRi-based synthetic circuits
A new study, published in Nature Communications by Schaerli lab, demonstrates the wide applicability of CRISPR interference for multistable and dynamic synthetic gene circuits.
Gene expression control based on CRISPRi (clustered regularly interspaced short palindromic repeats interference) has emerged as a powerful tool for creating synthetic gene circuits, both in prokaryotes and in eukaryotes; yet, its lack of cooperativity has been pointed out as a potential obstacle for dynamic or multistable synthetic circuit construction. The group of Yolanda Schaerli at the Department of Fundamental Microbiology, University of Lausanne now pioneered the use of CRISPRi to build a synthetic oscillator (“CRISPRlator”), bistable network (toggle switch) and stripe pattern-forming incoherent feed-forward loop (IFFL) in Escherichia coli populations. A mathematical modeling generated in collaboration with the group of Joerg Stelling at the Department of Biosystems Science and Engineering, ETH Zurich, suggests that unspecific binding in CRISPRi is essential to establish multistability. This work demonstrates the wide applicability of CRISPRi in synthetic circuits and paves the way for future efforts towards engineering more complex synthetic networks, boosted by the advantages of CRISPR technology.
Santos-Moreno, J., Tasiudi, E., Stelling, J., Schaerli, Y. Multistable and dynamic CRISPRi-based synthetic circuits. Nat Commun 11, 2746 (2020).
par Nassim Berberat-Farman