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The eternal battle between bacteria and viruses (article in Science by Delft/BN Stan Brouns lab and others)

[07-04-2017]

(By: TU Delft)
Science Magazine, published on Friday 7 April, features an article by TU Delft researchers and others on the CRISPR systems in bacteria and how they offer resistance to viruses.

Review
The publication in Science Magazine, written in collaboration with the laboratory of Peter Fineran of the University of Otago in New Zealand and Wageningen University & Research is a review article about how bacteria can adapt their ‘memory’ and resistance to bacteria by using what is known as the CRISPR-Cas adaptive immune system. ‘In the article, we highlight recent progress in understanding the molecular mechanisms in these kinds of bacterial defence systems,’ says researcher Stan Brouns from TU Delft’s Bionanoscience department.

Killing machines
Viruses can be seen as killing machines that are the archenemy of bacteria. A virus injects its DNA into a cell in order to try to take over control. In its defence, the bacterium leaps into action the moment a virus injects its genetic material. Proteins in the cell search for virus DNA, attach to it and send a signal to another protein. This arrives and cuts the virus DNA into shreds.

CRISPR
These proteins are capable of distinguishing between virus DNA and the DNA of the bacterium itself. This is because of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Researchers discovered these constantly repeating sequences of code (‘repeats’) in the DNA in the 1980s. It was only in 2005 that it was recognised that the DNA segments located between the repeats corresponded with the DNA of viruses.
‘Sometimes a bacterium survives an attack by a virus, perhaps because the virus was weakened, for example. In those rare cases, the bacterium seizes a trace of the virus’s DNA. By ‘unzipping’ its own DNA at the location of the repeats, the bacterium then builds the virus’s DNA into its own genetic code. The effect is comparable to how a vaccine works in that, from that moment on, the bacterium has that virus etched into its memory forever. If that same type of virus tries attacking that bacterium again, it recognises its assailant and can dispatch cutting proteins in its defence.’

Ethics
CRISPR systems now have much more significance than the mere biological curiosity described above. Since 2012, scientists have been able to use them to edit any DNA, by sending a piece of DNA to accompany the so-called Cas9 protein. CRISPR-Cas9 is now being used by thousands of research teams around the world to very precisely deactivate or overwrite particular genes. The technology has enormous medical and biotechnological potential.
‘There are many other CRISPR systems than the variant that uses the now famous Cas9 protein. Rather than being just a single tool, CRISPR-Cas is actually a whole kit full of different kinds of implements.’ This is why Brouns and his colleagues are so determined to get to the bottom of the biology behind CRISPR-Cas systems.
Moreover, the ethical issues in this field are becoming increasingly evident. ‘At a certain point, you cross the line of preventing diseases and move towards incorporating characteristics that people find desirable. That is something we have to consider with great care.’

More information 
The article ‘CRISPR-Cas: Adapting to change’ in Science: S.A. Jackson et al., Science 356, eaal5056 (2017). DOI: 10.1126/science.aal5056.
‘Tinkering under the bonnet of life’, about Stan Brouns’ research on CRISPR systems (Brouns Lab).

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