CRISPR, not a new savoury snack but an exciting tool for scientists-an introduction

An introduction to CRISPR in a short series on gene editing

CRISPR is a biological system scientists are exploiting using to edit genes in research. 

I  hear you  saying why, what, where and HOW??? Well grab some CRISPs and hold on tight for this whistle stop tour of CRISPR system!

Firstly, a gene is a short sequence of DNA- deoxyribonucleic acid. Hailed for being the blueprint or the code for life DNA is made up of two strands of four different nucleotides, adenine (A), cytosine (C), guanine (G) and thymine (T) which form a code for the production of proteins in the cell. Every three nucleotides (beads) on one strand form a code for an amino acid.

DNA made up of four nucleotides

In  some diseases there can be changes in this code of nucleotides, for example in cystic fibrosis there is a deletion of three nucleotides which form the code for the the 508th amino acid (phenylalanine) in a protein which lies across the membrane (enclosing) of cells. This is the molecular basis of cystic fibrosis and shows how genetic changes can have a huge impact on cell function. Hence being able to edit this genetic code could have huge implications on health and disease. To explore more about how the amino acid sequence affects proteins have a read of my previous blog post on protein folding and organisation.

What if we could change these errors in the code? How can we ensure that the DNA (which is so long) is edited in exactly the right place? What can we use to do this?

In comes CRISPR (Clustered regulatory inserted short pallindromic repeats-SUCH A mouthful) which was  co-discovered in 2012 by Professor Jennifer Doudna and  Emmanuelle Charpentier who were studying how prokaryotes (i.e bacteria etc) defend themselves against viruses and virus related microorganisms such as phages. Yes, bacteria does have its own form of immune system.

When a bacterium is attacked by a virus, the virus inserts its own genetic material which is then replicated by the bacterium and is used to make new viruses.
When a bacterium has a CRISPR system, it has sequences of identical DNA which are evenly spaced by DNA which is has a unique sequence. This spacer DNA is important as it matches up with viral DNA. 

This CRISPR system is associated with a set of genes called Cas (CRISPR assoicated genes) which encode for proteins that unwind and cut the DNA When a bacterium is infected by a virus and the viral DNA is inserted and the spacer DNA, so the CRISPR gene that matches the inserted viral DNA is copied into a transcript called CRISPR ribonucleic acid (crRNA). The crRNA fits into the Cas protein and this breaks up the viral DNA preventing the infection.

CRISPR system when viral DNA matches CRISPR spacer

When viral DNA is inserted into a bacterium that does not have a matching CRISPR spacer, a different kind of Cas protein is produced that copies this viral DNA to create a CRISPR spacer for the next time it infects as well as breaking down the viral DNA.

CRISPR system when viral DNA does not match CRISPR spacer

That is is the CRISPR system in a crisp packet! Scientists Professor Jennifer Doudna and  Emmanuelle Charpentier studies the CRISPR system in bacteria Streptococcus Pyogenes. This enabled them to develop a tool for gene editing.

Now you know a little bit more about the basic CRISPR system, sit tight for part 2 to explore how this system is used for gene editing and to think about the future implications.