What on earth is CRISPR?


Hello, lovelies!

It is officially post day!! Today's post is centred on that genetic editing technique that has kind of taken over headlines, generated a lot of public engagement on whether we have gone too far or not - CRISPR. To be honest with you, I am amazed at what this technique is able to do.  Then it hit me, that I do not actually know where this technique came from, it just suddenly appeared out of nowhere and took the world by storm. Have no fear after today's post you will have a better understanding of where the hell CRISPR came from. Enjoy. 


Molecular Biologists, Conservationists, Geneticists believe the discovery of CRISPR is the best thing, well - since sliced bread! With this technologies ability to modify wild and domestic populations, produce hypoallergenic eggs and possibly reverse extinction and bring back the woolly mammoth you could understand the excitement. However, there is a dark side to such technological advancements, CRISPR increases the risk of harmful biological agents being engineered. One question remains on the minds of many swept up by the CRISPR mayhem, what on earth is it?


CRISPR stands for clustered, regularly interspaced short palindromic repeats. Francisco Mojica, spotted these repeats when he was looking at the genome of a microbe known as Haloferax mediterranei. He found that there were 14 DNA sequences that repeated themselves and that they read the same forwards as they did backwards. Utterly transfixed by these repeating units he committed himself to learning more about their function and origins. In his lab, Franciso made the discovery that CRISPR was part of a sophisticated immune system found in bacteria.


Single-celled organisms such as Bacteria and Archaea are under constant threat from invading viruses. As it stands Viruses outnumber their victims ten to one leading to large scale losses in bacterial numbers every single day. In the face of such troubling odds, bacterias only choice for a chance at survival was to adapt and evolve defences against these genetic intruders. Bacteria and Archaea have done this very well with a range of weaponry, however, the most sophisticated system evolved belongs to those with the CRISPR-Cas system.


As it turns out, we share a similar immune response to bacteria. The CRISPR-Cas system used by bacteria and Archaea handles invading viruses in a way that mirrors how our immune system produces antibodies. Between each set of palindromic repeats in a bacterial genome, there are 'spacer' sequences. These sequences are inserted by CRISPR-associated proteins (Cas) and contain genetic remnants of viral invaders. Over time CRISPR-associated proteins build a genetic 'library' in the bacteria's genome. This library of past invasions aids the bacterium's fight against a virus that it has encountered before, by teaching Cas proteins to seek and destroy any genetic invaders (Viruses) with DNA matching the 'spacer' sequence.


Our immune system does a very similar method, the main difference being the scale through which it occurs. When our body is under attack by a pathogen, our immune response launches a counterstrike and eliminates the pathogen. After the attack phase of our response immune cells known as B Lymphocytes remain in our system, ready to remind our body how to deal with the pathogen should it invade again.


Bacteria with the CRISPR-Cas immunity must pay attention to what DNA they insert into the ‘spacer’ sequences. There are many similarities in viral DNA and host bacteria DNA,  as such the risk of inserting their own sequences into the ‘spacer’ would lead to suicide via the autoimmune response.  In single-celled Prokaryotes genetic storage is a problem due to limited available space it would prove difficult to store information on every viral invasion experienced.


When 'spacer' sequences were looked at in greater detail it was found that the sequences were from viruses never documented before. This finding shocked the scientific community as it may highlight just how little is known about the diversity of viruses. On the other hand, some argue that these sequences could belong to viruses that are now extinct, or to viruses that have now mutated their sequence so that they remain undetected by CRISPR. Ultimately, CRISPR-Cas system is likely to be more of a hindrance if the latter is true.  Many ‘spacer’ sequences would be a waste of space if they code for viruses that have gone extinct or have changed their sequence.


CRISPR is proving to be extremely popular for our species, but for Prokaryotes not so much. More than 90% of Archaea employ this system, in contrast to a third of bacteria investing in such a system. Issues with memory storage, mean that bacteria in contact with many viruses are likely to suffer more from ‘genetic burdens’ and not reap the rewards of CRISPR.

Molecular Biologists, Conservationists, Geneticists believe the discovery of CRISPR is the best thing, well - since sliced bread! With this technologies ability to modify wild and domestic populations, produce hypoallergenic eggs and possibly reverse extinction and bring back the woolly mammoth you could understand the excitement. However, there is a dark side to such technological advancements, CRISPR increases the risk of harmful biological agents being engineered. One question remains on the minds of many swept up by the CRISPR mayhem, what on earth is it?


CRISPR stands for clustered, regularly interspaced short palindromic repeats. Francisco Mojica, spotted these repeats when he was looking at the genome of a microbe known as Haloferax mediterranei. He found that there were 14 DNA sequences that repeated themselves and that they read the same forwards as they did backwards. Utterly transfixed by these repeating units he committed himself to learning more about their function and origins. In his lab, Franciso made the discovery that CRISPR was part of a sophisticated immune system found in bacteria.


Single-celled organisms such as Bacteria and Archaea are under constant threat from invading viruses. As it stands Viruses outnumber their victims ten to one leading to large scale losses in bacterial numbers every single day. In the face of such troubling odds, bacterias only choice for a chance at survival was to adapt and evolve defences against these genetic intruders. Bacteria and Archaea have done this very well with a range of weaponry, however, the most sophisticated system evolved belongs to those with the CRISPR-Cas system.


As it turns out, we share a similar immune response to bacteria. The CRISPR-Cas system used by bacteria and Archaea handles invading viruses in a way that mirrors how our immune system produces antibodies. Between each set of palindromic repeats in a bacterial genome, there are 'spacer' sequences. These sequences are inserted by CRISPR-associated proteins (Cas) and contain genetic remnants of viral invaders. Over time CRISPR-associated proteins build a genetic 'library' in the bacteria's genome. This library of past invasions aids the bacterium's fight against a virus that it has encountered before, by teaching Cas proteins to seek and destroy any genetic invaders (Viruses) with DNA matching the 'spacer' sequence (image below).

Image Source

Our immune system does a very similar method, the main difference being the scale through which it occurs. When our body is under attack by a pathogen, our immune response launches a counterstrike and eliminates the pathogen. After the attack phase of our response immune cells known as B Lymphocytes remain in our system, ready to remind our body how to deal with the pathogen should it invade again.


Bacteria with the CRISPR-Cas immunity must pay attention to what DNA they insert into the ‘spacer’ sequences. There are many similarities in viral DNA and host bacteria DNA,  as such the risk of inserting their own sequences into the ‘spacer’ would lead to suicide via the autoimmune response.  In single-celled Prokaryotes genetic storage is a problem due to limited available space it would prove difficult to store information on every viral invasion experienced.


When 'spacer' sequences were looked at in greater detail it was found that the sequences were from viruses never documented before. This finding shocked the scientific community as it may highlight just how little is known about the diversity of viruses. On the other hand, some argue that these sequences could belong to viruses that are now extinct, or to viruses that have now mutated their sequence so that they remain undetected by CRISPR. Ultimately, CRISPR-Cas system is likely to be more of a hindrance if the latter is true.  Many ‘spacer’ sequences would be a waste of space if they code for viruses that have gone extinct or have changed their sequence.


CRISPR is proving to be extremely popular for our species, but for Prokaryotes not so much. More than 90% of Archaea employ this system, in contrast to a third of bacteria investing in such a system. Issues with memory storage, mean that bacteria in contact with many viruses are likely to suffer more from ‘genetic burdens’ and not reap the rewards of CRISPR.

There you have it a brief introduction to CRISPR origins and what it is. Exploiting CRISPR-Cas's ability to insert genes into genomes of organisms make it beneficial for those who to engineer organisms, whether it be activating gene expression or correcting the 'typos' that cause the onset of genetic diseases.

That is all for this week my lovely people, have an awesome weekend!
Science in the City
xoxo

Image sources for header image:

Information gathered from Nature magazine and the Broader Institute.

1 comment

  1. Like your article, content is very good, next time will come again.

    Flat earth forum

    ReplyDelete

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