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They are both feared pathogens and a promising source of new drugs fungi of the genus Fusarium. Spreading worldwide, they can cause life-threatening infections. At the same time, they yield a wide diversity of natural products, offering a largely untapped source of new antiinfectives. The new research project FUSION at the Leibniz-HKI is tackling this dual challenge by combining genetic research on fungi with robot-assisted drug discovery. For the project, the two junior research groups led by Slavica Janevska and Luzia Gyr are pooling their expertise to develop new strategies against pathogenic Fusarium species and to unlock the potential of these fungi for the discovery of novel compounds.
Filamentous fungi of the genus Fusarium belong to the rare group of so-called trans-kingdom pathogens: they can infect plants, animals, and humans alike. They pose a significant risk particularly to immunocompromised patients, but can also cause infections of the body surface in otherwise healthy individuals. The World Health Organization (WHO) has therefore classified Fusarium species as particularly problematic pathogens.
“Fungal infections are on the rise worldwide, yet there are hardly any new drugs in development,” explains Dr. Luzia Gyr, who heads the junior research group Robotic-assisted Discovery of Antiinfectives. “This makes it all the more important to discover new bioactive molecules and to lay the foundation for future therapies.” In the case of Fusarium, their pronounced natural resilience further complicates treatment. “They are resistant to many commonly used antifungal drugs,” adds Dr. Slavica Janevska, head of the junior research group (Epi-)Genetic Regulation of Fungal Virulence. “There is an urgent need for new therapeutics.”
Both researchers successfully lead independent junior research groups. Through FUSION, they are now bringing together two complementary scientific approaches to discover new antifungal agents – targeting Fusarium, but also those derived from Fusarium.
Tracking down new compounds together
Gyr’s group develops automated methods to systematically test natural products and synthetic molecules for their activity against fungal infections – including compounds that are often overlooked by conventional methods. At the core of this work is the JenXplor robotic platform, which enables high-throughput screening experiments. “With our platform, we can test thousands of compounds under different conditions. We also implement new experimental approaches that are not feasible in conventional laboratory setups,” explains Gyr. She adds: “To achieve this, we develop test systems and combine automated experiments with comprehensive data analysis to identify potential drug candidates at an early stage.”
Within FUSION, her team has, for the first time, integrated filamentous human-pathogenic fungi into the automated platform. Their filamentous growth and spore formation pose particular challenges for the system, but these could be overcome by adapting procedures. The researchers also make use of the extensive natural product library at the Leibniz-HKI. “We aim to systematically test this collection against Fusarium,” says Gyr. “It is possible that it already contains compounds that are effective against these fungi.”
Janevska and her team investigate the genetic basis of Fusarium virulence, as well as the biosynthesis of its natural products. Using genomic data, they identify so-called biosynthetic gene clusters: the genetic blueprints responsible for producing specific molecules. “We now know that many of these gene clusters are not active at all under standard laboratory conditions,” says Janevska. “By specifically modifying growth conditions or co-cultivation with other microorganisms, we aim to activate these ‘silent’ metabolic pathways and thereby reveal new natural products.”
Fusarium as a treasure trove
As dangerous as Fusarium fungi can be, they also appear highly promising as a source of new active compounds. Numerous species produce a wide range of so-called secondary metabolites – chemical compounds that, in nature, serve functions such as communication or defense against competing microorganisms. “These molecules can provide a valuable starting point for new drugs,” says Janevska. “However, this potential is far from being fully explored.”
By combining genetic analysis, microbiological and chemical expertise, and automated screening approaches, FUSION unlocks new possibilities in this area. For example, different cultivation conditions can be systematically compared, or new fungal isolates can be examined – for example from the Thuringia region.
Interdisciplinarity as the key
Both group leaders agree that the scientific challenges surrounding Fusarium can only be tackled jointly. “The project is highly interdisciplinary,” says Gyr. “Our groups bring different perspectives to the table that complement each other perfectly.” Janevska also sees great potential in the collaboration: “We can learn a great deal from each other. Combining our expertise opens up new avenues for us, both to better understand the biology of Fusarium species and to develop new strategies to combat them. It is also valuable to have a sparring partner at eye level when it comes to developing our academic careers.”
In the long term, the researchers aim not only to identify new active compounds but also to establish processes that can be applied to other microorganisms. “In the best-case scenario, we will discover a molecule with an entirely new mode of action against Fusarium,” says Gyr. “But even if a compound is not suitable for human medicine, it could, for example, be used in plant protection.”
Funding
FUSION is funded by the Free State of Thuringia with resources from the European Social Fund Plus (ESF+). The project is accompanied by an industrial advisory board that focuses on the future application of the research results. The board comprises representatives from Analytik Jena, Basilea Pharmaceutica International, Bright Giant, Carl Zeiss Microscopy, and Jena Bioscience.
Dr. Luzia Gyr
Head of Department
Robotic-assisted Discovery of Antiinfectives
luzia.gyr@leibniz-hki.de
https://www.leibniz-hki.de/en/robotic-assisted-discovery-of-antiinfectives.html
Dr. Slavica Janevska
Head of Department
(Epi-)Genetic Regulation of Fungal Virulence
slavica.janevska@leibniz-hki.de
https://www.leibniz-hki.de/en/epi-genetic-regulation-of-fungal-virulence.html
Fusarium in focus: Bright-field microscopy images from the JenXplor robotic platform show uninhibite ...
Copyright: Leibniz-HKI
Junior group leaders Luzia Gyr (left) and Slavica Janevska (right) combine their expertise in the FU ...
Quelle: Anna Schroll
Copyright: Leibniz-HKI
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