Microbiology Society Prize Medal: Dr Christoff Fellmann
Posted on June 12, 2019 by Ellen Hinkley
On the second day of Annual Conference 2019, Dr Christof Fellmann presented the Microbiology Society Prize Medal Lecture on behalf of Professor Jennifer Doudna. Professor Doudna was awarded the prize in recognition for her fundamental work on CRISPR–Cas systems – used by bacteria and archaea as adaptive immunity against foreign genetic elements such as viruses. The Prize Medal is awarded annually to an outstanding microbiologist who is a global leader in their field and whose work has had a far-reaching impact beyond the discipline of microbiology.
Dr Fellmann introduced his lecture, titled ‘Discovering and developing next-generation CRISPR-Cas tools’, by providing an overview of CRISPR-Cas. He explained that it was a tool to rewrite of the genetic code with many current and potential uses in molecular biology and precision medicine.
In his overview, Dr Fellman explained that when bacteria are attacked by viruses known as bacteriophages (phages), they are able to cut up the DNA and integrate it into their own genomes. He described how, upon a secondary attack, the bacteria’s CRISPR-Cas machinery acts as an immune system, allowing the bacteria to quickly recognise and destroy the phage DNA. The ‘Cas’ part of CRISPR-Cas is an enzyme, which cuts the phage’s DNA at specific target sites.
Dr Fellmann went on to introduce the idea of anti-CRISPRs (Acrs), which are thought to be made by the bacteriophages that attack the bacteria to evade this immune response. He explained that some bacteria end up with sections of DNA in their genomes which are recognised by the CRISPR-Cas system as phage DNA, but are in fact they bacterial, causing the bacterium to attack itself. These are known as ‘self-targeting genomes’ and bacteria with these genomes use Acrs to avoid self-destruction.
The Doudna lab identified bacteria with these self-targeting genomes to discover new Acrs. Once these had been discovered, they moved on to looking at the mechanisms of the Acrs and found that they work in a variety of ways, targeting different parts of the CRISPR-Cas machinery.
Once he’d described how the lab had investigated the details of the mechanisms of Acrs, Dr Fellmann moved on to explain how the researchers tackled the task of moderating Cas, as the molecule is naturally always active. Through a series of experiments, they found that they could create an inactive form of Cas9, referred to as ‘vigilant ProCas9’ which could be activated by a type of molecule that cuts proteins called a protease. This, Dr Fellmann proposed, provides a way to use CRISPR-Cas in specific cells or tissues, as it could be activated at the target site, not affecting any surrounding cells or tissues during delivery.
Dr Fellmann concluded the lecture by briefly discussing the potential use of Cas9 molecules as base editors, meaning that they cut only one strand (as opposed to both strands) of the DNA molecule. This would avoid the risks of damage to cells associated with double stranded breaks in the DNA.
You can view Professor Fellmann’s full lecture below: