Researchers Successfully Map Most Extensive Visualization of A Complex CRISPR System

A research team at the University of Copenhagen’s Faculty of Health and Medical Sciences has successfully visualized the largest and most complex CRISPR system – a system that may exhibit the potential applications in biomedicine and biotechnology. The study has been published in the Molecular Cell, on Tuesday.

The CRISPR technology is used to edit genes and has transformed the research and scientific world. The CRISPR – Cas stands for clustered regularly interspaced short palindromic repeats. Cas stands for CRISPR-associated protein. To date CRISPR-Cas9 is probably the most well-known of the CRISPR systems with one associated protein Cas9, being used for gene editing. CRISPR-Cas9 is likely the most known CRISPR-system and popularly known as the gene scissor. There are numerous CRISPR systems available. The research team at the University of Copenhagen (UCPH) have successfully mapped and analysed the atomic structure of one of the most complex CRISPR systems to date.


“We have solved the largest and most complicated CRISPR-Cas complex seen so far. We now understand how this system works on a molecular level,” says co-author Guillermo Montoya, who is Professor at the Novo Nordisk Foundation Center for Protein Research (NNF CPR), UCPH.

In the study, the scientists extensively studied the complex structure called Cmr-β, which belongs to the subgroup of so-called type III-B CRISPR-Cas complexes.  The study says that the CRISPR is a complex system found in bacteria, among other organisms, and it is believed to be involved in the bacteria’s immune system. In the new study, it plays an integral part in the constant fight against invading phages, a virus that attacks bacteria. In the current study, researchers have studied the role of the Cmr’s complex in the immune system and elucidated further the underlying mechanisms behind its immune response against phages and how it is regulated.

“Our findings, in collaboration with the She group at the Faculty of Sciences, highlight the diverse defence strategies of type III complexes. We have also identified a unique subunit called Cmr7, which seems to control the complex activity, and we further believe that it may defend against prospective viral anti-CRISPR proteins,” says co-author Nicholas Heelund Sofos, postdoc at NNF CPR.

The potential applications of the Cmr system mapped by the researchers in the new study includes the ability among other things to the remove single-stranded RNA and DNA. Though it will be very difficult to use for gene editing like CRISPR-Cas9. Yet, it is too large and complex. However, in the future, it may still be key to understand the immune response of bacteria and it could have some use in the fight against antibiotic resistance.

The study author says that it is presumed that this complex plays an important role in the fight between bacteria and phages. Antibiotic resistance comes from this type of fight. Therefore, their results may constitute a considerable amount of an important knowledge for fighting antibiotic resistance. In the study, the advanced technique of the cryo electron microscopy — also called CryoEM, has been used to outline the system.

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