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Faculty of Science researchers Bas van Ravensteijn and Markus Weingarth have each been awarded an ERC Proof of Concept Grant. Weingarth will use the grant to further combat bacterial resistance to antibiotics. Van Ravensteijn aims to enhance the precision and effectiveness of gene therapy.

ERC Proof of Concept Grants are designed to help researchers turn their scientific discoveries into real-world applications. The grants support follow-up work from existing ERC-funded research and allow scientists to explore the societal or commercial value of their findings. The grants are €150,000 each.

Project: In vitro & biodistribution analysis of morphology-controlled polymeric gene delivery nanocarriers (POLYMORPH)
Dr. Bas van Ravensteijn

Supported by the grant, Bas van Ravensteijn and his research partners are set to study how the molecules used in gene therapy end up in the right place.

Gene therapy aims to correct errors in a patient’s DNA, offering the potential to cure genetic disorders. But for the treatment to work, the therapeutic molecules, usually RNA or DNA, must be delivered to the right part of the body.

Because RNA and DNA molecules are relatively unstable, they are packaged in so-called nanocarriers. Right now, these are often lipid nanoparticles, tiny globules of fat. However, when these lipid nanoparticles are introduced into the bloodstream, they tend to accumulate in the liver. That is helpful if you are targeting a genetic liver disease, but limits treatment of other organs like the brain.

Van Ravensteijn and colleagues previously developed a new method for creating nanoparticles loaded with DNA or RNA made from polymers. These particles can be produced in a range of shapes. Now, the team plans to track where polymer particles of different shapes end up in the body.

“Our main inspiration comes from viruses,” Van Ravensteijn explains. “They are really good at efficiently delivering their RNA or DNA. They come in all sorts of shapes and end up in different organs. We want to see if we can mimic that.”

Van Ravensteijn and colleagues collaborate with a range of partners, including clinicians, industry experts, and specialists in drug regulation. Van Ravensteijn: “We are still in the early stages. Collaborating increases the chances that our work will eventually lead to real-world applications.”

Project: Structural biology tools for Antibiotic Research (STAR)
Dr. Markus Weingarth

In this project, biochemist Markus Weingarth aims to tackle the rising threat of antimicrobial resistance, which is projected to cause up to 10 million deaths annually by 2050. STAR will help researchers better understand how powerful antibiotics attack bacteria. This knowledge is crucial for developing safer and more effective drugs.

Weingarth’s project focuses on improving a highly specialized technique called Solid-State Nuclear Magnetic Resonance (NMR). This tool lets researchers ‘see’ at the molecular level how antibiotics interact with bacterial membranes.

A key challenge in this field is producing a special form of fatty molecules called lipids, which are the building blocks of bacterial membranes. The lipids are labeled with isotopes, which allows researchers to track them in extremely high detail using NMR. However, these labeled lipids are very difficult to produce in sufficient quantity and purity. 

“These lipids are not available commercially, so we need to make them ourselves,” says Weingarth. “With this grant, we can now scale up our current production and dramatically improve the sensitivity of our experiments.”

The potential impact of STAR goes far beyond antibiotics. The labeled lipids could help researchers study a wide range of biological processes, for instance how disease-related proteins behave. Another promising application is gaining insight into how lipid nanoparticles (like those used in mRNA vaccines) function in our body. The project will also explore commercial pathways and partnerships, to make the lipids available for researchers worldwide.