Mechanisms Mapped in the largest CRISPR System
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Mechanisms Mapped in the largest CRISPR System

In a new study, researchers from the University of Copenhagen have visualized the largest and most complex CRISPR system. The researchers believe that the system may have potential applications in biotechnology and biomedicine.

When CRISPR technology, used to edit genes was first introduced, it revolutionized the scientific world. CRISPR-Cas9, popularly known as the gene scissor, is just one out of the many various CRISPR systems that exist and is likely the most known CRISPR-system.

Now, the atomic structure of one of the most complex CRISPR systems so far has been mapped and analyzed by researchers from the University of Copenhagen (UCPH).

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

A complex belonging to the subgroup of so-called type III-B CRISPR-Cas complexes, called Cmr-β, has been studied by the researchers. The scientific journal Molecular Cell published this study’s results.

CRISPR is a system found in bacteria and is involved in the immune system of bacteria. The main role played by it here is in the

constant fight against a virus that attacks bacteria, the invading phages.

The role of Cmr in the immune system, the mechanisms behind its immune response against phages, and how it is regulated has been studied by the researchers in the new study.

A postdoc at NNF CPR and co-author Nicholas Heelund Sofos said, “The diverse defense strategies of type III complexes are highlighted in our findings, in collaboration with the She group at the Faculty of Sciences. Cmr7, a unique subunit called, which appears to control the complex activity has also been identified.”

Potential applications

Among other things, single-stranded RNA and DNA can be removed by the Cmr system mapped by the researchers in the new study. Using it for gene editing like CRISPR-Cas9 will be very difficult.

It is too complex and big. However, in the future, it could have some use in the fight against antibiotic resistance and it may still be key to understand the immune response of bacteria.

In the fight between bacteria and phages, which leads to antibiotic resistance, this complex plays an important role. Thus, for fighting antibiotic resistance, our results may constitute an important knowledge.”

Guillermo Montoya says, “As the complex might also have therapeutic potential, we may be able to use this in the future for diagnostics or a health problem that we have not yet come across. Finding an application for this system is our goal now.”

To outline the system, the advanced technology cryo-electron microscopy, also called CryoEM was used by the researchers. At the University of Copenhagen, all research and data collection was conducted. The Independent Research Fund Denmark and the Novo Nordisk Foundation, among others funded this study.

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Mechanisms Mapped in The Largest CRISPR System by University of Copenhagen Researchers