Researchers map mechanisms in the largest CRISPR system

Date:
July 29, 2020
Source:
University of Copenhagen The Faculty of Health and Medical Sciences
Summary:
The largest and most complex CRISPR system has been visualized
by researchers in a new study. The system may have potential
applications in biomedicine and biotechnology, the researchers
believe.



FULL STORY ==========================================================================
The largest and most complex CRISPR system has been visualized by
researchers from the University of Copenhagen in a new study. The system
may have potential applications in biomedicine and biotechnology, the researchers believe.


========================================================================== CRISPR technology can be used to edit genes and revolutionised the
scientific world when it was first introduced. CRISPR-Cas9 is likely
the most known CRISPR-system and popularly known as the gene scissor.

That is just one out of the many various CRISPR systems that exist. Now researchers from the University of Copenhagen (UCPH) have mapped and
analysed the atomic structure one of the most complex CRISPR systems
so far.

"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.

The researchers have studied a complex called Cmr-b, which belongs to the subgroup of so-called type III-B CRISPR-Cas complexes. The new results
have been published in the scientific journal Molecular Cell.

Fights against phages CRISPR is a system found in bacteria, among other organisms, and it is involved in bacteria's immune system. Here it plays
a main role in the constant fight against invading phages, a virus that
attacks bacteria.



==========================================================================
In the new study, the researchers have studied Cmr's role in the immune
system and delved into the 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.

Potential applications The Cmr system mapped by the researchers in the new study can among other things remove single-stranded RNA and DNA. Though
it will be very difficult to use for gene editing like CRISPR-Cas9.

It is too big and complex. But 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.



========================================================================== "This complex plays an important role in the fight between bacteria
and phages.

Antibiotic resistance comes from this type of fight. Therefore, our
results may constitute an important knowledge for fighting antibiotic resistance." "The complex may also have therapeutic potential. In the
future, we may be able to use this for diagnostics or a health problem
we may not even have seen yet.

Now, our goal is to look for an application for this system," says
Guillermo Montoya.

The researchers used the advanced technology cryo electron microscopy
-- also called CryoEM -- to outline the system. All research and data collection was conducted at the University of Copenhagen.

CRISPR-Cas * CRISPR stands for clustered regularly interspaced short palindromic repeats.

Cas stands for CRISPR-associated protein.

* CRISPR-Cas9 is probably the most well-known of the CRISPR systems
and can be used for gene editing. One protein is associated with the
system: Cas9.

* Many small proteins are associated with the Cmr-b system outlined by
the researchers in the new study.


========================================================================== Story Source: Materials provided
by University_of_Copenhagen_The_Faculty_of_Health_and
Medical_Sciences. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Nicholas Sofos, Mingxia Feng, Stefano Stella, Tillmann Pape, Anders
Fuglsang, Jinzhong Lin, Qihong Huang, Yingjun Li, Qunxin She,
Guillermo Montoya. Structures of the Cmr-b Complex Reveal
the Regulation of the Immunity Mechanism of Type III-B
CRISPR-Cas. Molecular Cell, 2020; DOI: 10.1016/j.molcel.2020.07.008 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200729114837.htm

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