With the second grant from the lab into the application

CRISPR technologies have revolutionized genome editing: they can modify virtually any DNA—at any genomic site in any organism. However, in many cases, the procedure is inefficient, and the quantity of modified cells is very low. To identify and isolate cells with the desired edits, extensive screening can be required. Relief could come from a mechanism recently discovered by a research team led by the Helmholtz Institute Würzburg. The further exploration of this mechanism is now supported by the European Research Council (ERC) through an ERC Proof of Concept Grant of 150,000 euros.

As part of a project already funded by an ERC Consolidator Grant, the team led by department head Chase Beisel is researching CRISPR-Cas systems at the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI), a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität (JMU). These systems, which form the natural immune defense of bacteria against viruses, are the foundation of CRISPR technologies and are commonly referred to as “gene scissors.”

The researchers identified a new mechanism that kills unmodified cells while sparing modified ones. “The method relies on the Cas12a2 nucleases we recently characterized together with Benson Hill, Inc. (Missouri) and Utah State University in the U.S., and can be described as programmable counter-selection: undesired cells can—in theory—be easily and specifically removed,” Chase Beisel, who also holds a professorship at the Faculty of Medicine of the JMU, explains. “This would provide much-needed relief in screening for various applications of genome editing,” adds the CRISPR expert.

In the now-funded project, Beisel will conduct proof-of-concept experiments together with researchers at Utah State University, the University of Utah and BRAIN Biotech AG. The researchers will evaluate the mechanism in human cells and investigate which editing applications would benefit most from the method.

“The associated tasks build on my extensive work at the interface of CRISPR biology and technologies. I ultimately aim to translate a novel biological insight from my group’s ERC project into an innovative foundational technology that could find broad application in genome editing,” he summarizes. If successfully developed, the method could simplify the generation of cell-based therapies and accelerate the generation of edited cells for studying the mechanistic basis of human diseases.

From basic research to society

“This is the fifth time in six years HIRI researchers have received a prestigious ERC grant. Such funding by the European Research Council is highly competitive and reserved for the most innovative research. I am delighted that Chase Beisel and his team can take another important step from basic RNA research towards application with this new grant,” says HIRI director Jörg Vogel.

The Proof of Concept funding line

The ERC Proof of Concept (PoC) funding line is aimed at ERC grant holders who wish to establish proof of concept of an idea that was generated in the course of their ERC projects. The grants aim at facilitating exploration of the commercial and social innovation potential of ERC-funded research.

The European Research Council

The European Research Council (ERC), set up by the European Union in 2007, is the premier European funding organization for excellent frontier research. It funds creative researchers of any nationality and age, to run projects based across Europe. The ERC offers four core grant schemes: Starting Grants, Consolidator Grants, Advanced Grants and Synergy Grants. With its additional Proof of Concept Grant scheme, the ERC helps grantees to explore the innovation potential of their ideas or research results.

Helmholtz Institute for RNA-based Infection Research

The Helmholtz Institute for RNA-based Infection Research (HIRI) is the first institution of its kind worldwide to combine ribonucleic acid (RNA) research with infection biology. Based on novel findings from its strong basic research program, the institute’s long-term goal is to develop innovative therapeutic approaches to better diagnose and treat human infections. HIRI is a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität Würzburg (JMU) and is located on the Würzburg Medical Campus.