Interrogating the biological fundamentals of CRISPR to better understand and treat infections

ERC Consolidator Grant for HIRI researcher Chase Beisel

For his research project "CRISPR Combo", Prof. Chase Beisel receives a five-year grant of two million euros. He wants to search for combinations of relevant key genes of pathogens in order to be able to specifically eliminate these in the future with the help of tailor-made CRISPR genetic scissors. Chase Beisel heads the “Synthetic Biology of RNA” research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, a branch of the Helmholtz Centre for Infection Research (HZI) in Braunschweig and run in collaboration with the Julius-Maximilians-Universität in Würzburg. With the Consolidator Grants, the European Research Council (ERC) promotes research by up-and-coming scientists in Europe.

CRISPR is a word on everyone’s lips at the moment. Although it sounds somewhat crispy and delicious, it is in fact inedible – it is actually one of the most promising tools of genetic engineering. CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats”. These short DNA segments in the genome of bacteria are named after their regular pattern of repeating and mirrored sequences. They act as effective virus defence systems for bacteria. Copies of the CRISPR DNA exist in the form of RNA fragments in the cell. In the event of a viral attack, where a virus injects its DNA into a bacterium, the defence mechanism is triggered: The proteins, which include Cas9, is called to action and compares the sequence of the foreign DNA with that of the CRISPR RNA fragments. If it finds a matching counterpart, Cas9 cuts the foreign virus DNA, thus rendering the intruder harmless. The CRISPR–Cas9 system is therefore also known as genetic scissors and is now used for genome editing. DNA sequences can be specifically cut and modified in the laboratory using custom-designed CRISPR gene scissors, for example for the development of improved crops or medicines, for the manufacture of industrially used microorganisms, and in human cells for treating genetic diseases.

American chemical engineer Chase Beisel dedicated himself to CRISPR research around nine years ago. “We have an incredibly powerful genetic engineering tool at our disposal,” says Beisel. “In order to fully and safely utilise its potential in the future, it is important that we better understand the basic biological relationships of CRISPR complexes in bacteria.” The bacterial immune system can evidently learn new things and arm itself against other attackers by quickly integrating parts of foreign DNA into its own genome. CRISPR arrays encode the memory of previous infections and enable multiple intruders to be attacked simultaneously. How exactly these advanced CRISPR complexes are created, which criteria are used for selecting new sequences and which key genes of the attacker are thus rendered ineffective are not yet fully understood. This is exactly where Beisel’s current research project “CRISPR Combo” aims to start, addressing the unanswered questions. “In addition to researching the biological fundamentals of CRISPR arrays in bacteria, we would also go one step further in the direction of a genetic application of CRISPR arrays,” says Beisel. “To do this, we will use designed CRISPR arrays to target multiple genes at once in pathogens, thereby identifying combinations that most drive infections and providing new drug targets.”

In 2018, Beisel moved from the Department of Chemical and Biomolecular Engineering at the North Carolina State University in Raleigh (USA) to the HIRI in Würzburg, where he has been the head of the “RNA Synthetic Biology” research group for two years now. His twelve-person team consists of postdocs, doctoral candidates, technicians and students. “The funding from the ERC means I can confidently add four members to the team – that is really fantastic,” says Beisel. “The ERC Grant is an important milestone for me personally. Making the leap to Germany to join the HIRI was absolutely the right decision, and I am delighted about this funding. It enables me to dedicate my research to a topic that fascinates me and at the same time offers significant benefits for society as a whole.”

ERC Consolidator Grant:
The ERC Consolidator Grant funds promising scientists at the beginning of their independent careers. The funding enables the establishment and strengthening of their own research groups.

Author: Nicole Silbermann