CRISPR and Microbiology

Posted on October 12, 2020   by Professor David Grainger

Last week, the 2020 Nobel Prize in Chemistry was awarded to Professors Emmanuelle Charpentier and Jennifer Doudna for their work on the genetic editing tool CRISPR-Cas9. In this blog, Professor David Grainger discusses some of the earliest research on CRISPR-Cas9 published in our flagship journal Microbiology.

CRISPR (clustered regularly interspaced short palindromic repeats) are sections of DNA now known to encode systems that protect bacteria from invading viruses (bacteriophages). Understanding how these systems work has been an important standalone basic science endeavour. More recently, harnessing CRISPR has opened the door to precision genome editing across all of life’s domains. This week, these breakthroughs were recognised by the Nobel Committee who awarded the prize for chemistry to Emmanuelle Charpentier and Jennifer Doudna.

Now known to occur in diverse prokaryotes – encompassing both the bacteria and archaea – CRISPR regions were first reported in the late 1980s for bacteria, and early 1990s for archaea. Long viewed as nothing more than a sequence oddity, the function of these sequences remained mysterious for almost two decades. In the mid 2000’s, three papers were published in Microbiology that subsequently became seminal to the field. Here, we discuss the findings and implications of these studies. 

Until 2005, it was not appreciated that the spacer regions of CRISPRs were derived from foreign DNA (i.e. that of bacteriophages). Clearly, understanding this was crucial to subsequently deciphering the function of these systems and the associated molecular mechanisms. Around this time, several papers from different laboratories independently reported the ‘alien’ nature of CRISPR spacer DNA. Two such papers, from the laboratories of Gilles Vergnaud and Dusko Ehrlich, were published in Microbiology. Along with the contemporaneous findings of Francis Mojica, the first researcher to fully characterise a CRISPR locus in 1993, these papers represented a step change in our understanding of CRISPR systems. The hypothesis that CRISPRs were indicative of a prokaryotic adaptive immune system was born.

At the time, these findings were deemed controversial and published anecdotes from the authors describe resistance from the scientific community. Over the next decade, laboratories the world over joined the race to understand and exploit CRISPR. Francis Mojica remained at the forefront of these efforts and chose Microbiology as the venue for his 2009 paper describing the role of proto-spacer adjacent motifs (PAMs). Mojica published further studies of Escherichia coli CRISPR systems in Microbiology at the end of the decade. 

Read the articles discussed in the blog:

CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies

Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin

Short motif sequences determine the targets of the prokaryotic CRISPR defence system

Diversity of CRISPR loci in Escherichia coli

Find out more about CRISPR-Cas9 in our explainer video:

What is CRISPR-Cas?