Fungal Metabolites, Epigenetics, and Microbiome Structuring

This research area explores how fungal secondary metabolites influence microbiome composition and host interactions, shaping disease outcomes. It combines genetic and epigenetic analyses with studies of host–pathogen dynamics to understand the regulation of fungal virulence and its impact on immune evasion and infection progression.

The independent junior group (Epi-)Genetic Regulation of Fungal Virulence (EPI) focuses on opportunistic human pathogens of the genus Fusarium, using F. oxysporum as a model in the lab. Fusaria are remarkable trans-kingdom pathogens, being able to infect plants, animals, and humans. Little is known about how this important group of pathogens can proliferate in the mammalian host and which virulence factors contribute to this. We are currently tackling this question by assessing the species diversity in clinical, indoor, and environmental samples, followed by long-read whole-genome sequencing. We are focusing on small and mobile accessory chromosomes which could contribute to host adaptation.

We welcome excellent applicants, motivated to contribute to one of our research interests:

• Fusarium virulence factors, and assessing their influence on infection in in vitro cell culture models.
• How secondary metabolites could contribute to opportunistic human infections, since Fusaria are known as some of the most prolific producers within the fungal kingdom. This line of research would support our active research project FUSION.
• How epigenetic regulation mechanisms, in particular histone modifications found within facultative heterochromatin, could contribute to the transcriptional control of the infection process and the adaptation to different hosts. Our recent publication in Nucleic Acids Research characterized facultative heterochromatic marks in the context of plant infection.

The Department Molecular and Applied Microbiology (MAM) focuses on the infection biology of human-pathogenic fungi, the ecological role of natural products in shaping microbiomes, and the development of biotechnological methods to discover and produce novel microbial compounds and therapies for infectious diseases.

Life-threatening infections by Aspergillus fumigatus affect more than 2 million individuals yearly. Infections result in high mortality due to diagnostic gaps, antifungal resistance, and poorly understood virulence. Previous studies have addressed isolated mechanisms without integrating infection dynamics, immunosuppression, therapy, and microbiome interactions. We hypothesize that the pathobiology of A. fumigatus emerges from a mosaic of criss-cross interactions in which multiple fungal virulence factors engage diverse host responses. Further, fungal proteins and secondary metabolites modulate the dynamics of the host response and defense based on the microbiome composition and both can affect the outcome of an infection. Dynamic immune-cell responses and inflammatory signatures are key for antifungal immunity, which also depends on the host genetics.

Methodologies include screening of A. fumigatus isolates, the use of an A. fumigatus knockout library, evaluation of the dynamics of the host–pathogen interaction, including the analysis of cells of the innate and adaptive immune system, multi-omics analyses, MALDI imaging, LC-MS/MS analyses, microbiome analyses, and mouse infection models.

We welcome excellent applicants, motivated to contribute to deciphering host–pathogen interactions and elucidating the role of fungal virulence factors, including the role of the microbiome and understanding mechanisms of antifungal resistance.