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Catalysing Change: Five new solution-oriented projects take aim at infectious diseases

Tackling big challenges requires daring ideas – and many of them. That is why the ‘Infectious Diseases Catalyst Grants’ focus on kickstarting exceptional research projects that can help us counter the growth of dangerous infectious diseases. In 2024, DKK 24 million was awarded to five exciting projects, and this February, the Catalyst Grants call for applications will open again for a second round.

In a time of increasing environmental instability, infectious diseases are a growing global threat with complex causes and no clear-cut solutions. In response, the Novo Nordisk Foundation launched the Catalyst Grants in 2024 to spur innovation and quickly test new ideas within three core themes: Antimicrobial resistance (AMR), invasive pathogenic fungi and harnessing innate immunity against airborne viral infections. Now, the first five projects are ready for launch.

A creeping danger
“The world is in desperate need for new and creative approaches to combat antimicrobial resistance,” says Poul Nielsen, Professor at the University of Southern Denmark, who is one of the recipients of a Catalyst Grant. AMR happens when microorganisms such as bacteria evolve to evade the antibiotics we have invented to counter infections. No new classes of antibiotics have been developed for treatment since 1987, and if nothing is done, AMR is expected to surpass all other causes of mortality by 2050.

Poul Nielsen’s project aims to re-design an overlooked class of antibiotics, namely the pleuromutilins. “By rationally designing new and innovative pleuromutilin derivatives, we hope to be able to specifically overcome a known resistance mechanism in bacteria,” says Poul Nielsen.

With another AMR-directed Catalyst Grant project, Lone Brøndsted, professor at the University of Copenhagen, wants to provide a biology-driven strategy using so-called “bacteriophages” to identify a broader selection of bacterial targets for antimicrobial design. “Phages are viruses that only infect and kill bacteria,” says Lone Brøndsted. “They offer a unique opportunity to discover novel targets as their proteins interact with diverse bacterial targets, causing the bacteria’s death.”

Deadly spores
Accounting for an estimated 2.5 million deaths a year, infectious diseases caused by dangerous, invasive pathogenic fungi are arguably even more neglected than AMR. Patients with weakened immune systems (such as people with chronic conditions like HIV or diabetes or undergoing cancer or transplant treatments) are especially vulnerable to invasive fungal infections. But we do not know nearly enough about these dangerous fungi and have a very limited amount of anti-fungal treatments in our arsenal.

In his Catalyst Grant project, Professor Daan van Aalten from Aarhus University wants to understand the proteins in one of the most invasive pathogenic fungi, namely Aspergillus fumigatus. “This work can ultimately lead to the identification of opportunities for the discovery of novel anti-fungal drugs,” says Daan van Aalten. In another project, Professor Daniel Wüstner from the University of Southern Denmark, wants to use novel imaging techniques combined with chemical and genetic screening to dissect the mechanisms underlying the resistance of the fungal Candida family to the group of antifungal drugs called polyenes. “In addition to radically changing our perception of the mechanisms by which polyenes interfere with cellular functions, we can potentially find new ways to target the otherwise treatment-resistant fungi,” says Daniel Wüstner.

Lessons from the pandemic
The COVID-19 pandemic highlighted the ongoing threat of respiratory pathogens and how our innate immune response is crucial for our defences. A promising strategy is to boost our innate immune system, and in his Catalyst Grant project, Rune Hartmann from Aarhus University aims to understand why, and how, some immune cells respond better than others to Interferon λ, an important signalling protein released by virally infected cells.

“The knowledge generated by this research could lead to a more effective, broadly active treatment against viral infections, useful for curbing future pandemics or treating novel emerging viruses,” says Rune Hartmann.

The 2024 call for Infectious Diseases Catalyst Grants was a first for the Novo Nordisk Foundation, but a new call for 2025 will be opening at the end of February, focusing on the same three themes. Importantly, to qualify for funding research projects should be use-inspired, with a direct focus on how the findings from each study can be applied to enable better solutions. Furthermore, while projects are required to be led by a main applicant from a research institution in Denmark, projects that include international co-applicants are also welcome.

Catalyst grants awarded in 2024:

· Daan van Aalten, Aarhus University; DKK 5,999,458 for the project: “Targeting the linchpins of Aspergillus fumigatus cell wall synthesis”

· Daniel Wüstner, University of Southern Denmark; DKK 5,972,368 for the project: “Dissection of sphingolipid-ergosterol interactions to combat polyene resistance in infectious Candida”

· Lone Brøndsted, University of Copenhagen; DKK 2,992,374 for the project: “TARGETs for sustainable antimicrobial design”

· Poul Nielsen, University of Southern Denmark; DKK 2,999,909 for the project: “Chemical optimization of pleuromutilin for broad antibacterial activity and decreased resistance”

· Rune Hartmann, Aarhus University; DKK 5,996,364 for the project: “Interferon λ driven antiviral resistance in lung macrophages – a new therapeutic option?”

Further information

Lars Hvidberg
Communications Specialist
[email protected]