Targeted cultivation of novel (natural product producing) bacteria from the deep-sea sponge Geodia barretti

This project is a part of the MARBLES EU consortium, which has the objective of utilizing marine microbes for both drug discovery and the sustainable production of fish and crops. According to the 2022 report from the Global Antimicrobial Resistance and Use Surveillance System (GLASS), there has been an increase in the percentage of infections caused by multi-drug resistant bacteria (MDR) worldwide. While certain "drugs of last resort" are still available, there is a pressing need for new bio-active compounds to strengthen our last lines of defense. Consequently, bacteria from underexplored environments have garnered significant interest as potential sources of novel chemical structures, making them particularly promising for further exploration.

Oceans, characterized by their unique conditions, provide one such environment that hosts a diverse range of bacteria with remarkable adaptations. This project focuses on deep-sea marine sponges, specifically Geodia barretti, which serve as habitats for bacteria from the depths of the ocean to prosper. These sponges harbor diverse microbiomes, predominantly comprised of uncultured taxa, and contain Biosynthetic Gene Clusters (BGCs) responsible for the production of natural products. Notably, a major proportion of the identified BGCs differ from known ones, suggesting the potential for discovering new and distinct secondary metabolites. The primary objective of this project is to isolate and identify novel bacteria from G. barretti, as these microbes have the potential to be talented chemists capable of producing unique compounds, including the anti-inflammatory compound barettin.

To achieve this objective, a combination of techniques will be employed. Firstly, metaomic data analysis and genome mining tools will be utilized to identify potential natural product producers within G. barretti's microbiome. Secondly, the bacteria of interest will be functionally annotated to predict selective media and optimal conditions for their cultivation. Thirdly, a range of both standard methods, such as simple liquid cultures, and novel approaches, such as reverse genomics, will be employed for culturing purposes. Finally, the isolated strains will be screened and the derived natural products will be characterized in terms of their activity against a panel of fish pathogens.

By employing these methodologies, the project aims to uncover and describe novel natural products derived from the isolated strains, with a specific focus on their efficacy against fish pathogens.

Potential BSc and MSc thesis project topics include:

• Computational annotation of Biosynthetic Gene Clusters' diversity (Natural product chemistry/Bioinformatics background preferred).
• Isolation of prominent natural product producers from Geodia barretti using different cultivation techniques.
• Functional characterization of nutritional requirements of selected bacteria (Microbial physiology background preferred).
• Comparative genomics of novel sponge-associated taxa (Bioinformatics background preferred).