MIDAS

The MIDAS project focuses on the discovery and development of novel sustainable sources of bioactive compounds for specific pharmaceutical applications. The overarching objective of the project will be to bring a targeted set of aquatic extremophile prokaryotic and eukaryotic microorganisms into long-term ex situ laboratory culture and to screen them for specific bioactivities via an integrated biodiscovery pipeline. The intention is to focus bioprospection on novel drug discovery in the anti-cancer field. The project is founded on the hypothesis that organisms living in these extreme environments have evolved a plethora of innovate metabolic strategies and are hence an extremely promising source of unusual metabolites that have applications in the biomedical domain. The project will involve the following interlinked and interdisciplinary activities: (1) Bioinformatic "virtual screening" to identify organisms/lineages possessing metabolic pathways for molecules of interest and determine recurrent species associations and the range of environmental conditions delimiting the distribution of species of interest; (2) This information will be used to downstream inform sampling campaigns with a focus on cold (Arctic) and extremely low nutrient (oligotrophic) marine environments, but also in conditions of extreme pH and/or salinity; (3) A variety of techniques will be used for isolating mono-specific or stable microbiome communities into ex situ culture, including state-of-the-art flow cytometric sorting and microfluidics methods which will be developed/refined during the project; (4) Existing medium- to high-throughput screening pipelines (in part developed in previous EU projects) will be used to screen bulk extracts of novel culture strains for target bioactivities; (5) For a selection of strains exhibiting promising bioactivities, the cultures will be characterized by sequencing the full genome and conducting laboratory experiments to optimize the growth of the strain and/or production of the metabolite of interest. Optimized culture conditions will be employed (at the laboratory scale) to produce sufficient biomass for initial product development steps; (6) Bulk extracts from biomass provided to the commercial partner(s) will be fractionated and tested in various well-characterized cell lines. R&D will then focus on preliminary structural characterization of the molecules of interest and of their mechanism of action (TRL3-5). The originality of the MIDAS project resides in the combination of world-leading expertise in culturing and characterization of aquatic microorganisms, informed by cutting-edge bioinformatics approaches, feeding into established bioprospecting pipelines to promote the efficient discovery of novel bioactive molecules from extremophile organisms that are an extremely promising, but as yet underexploited natural resource. The project will build upon strategic advances from previous EU projects such as PharmaSea (2012-2016), EMBRIC (2015-2019) and Nomorfilm (2015-2019) and involve significant methodological innovation, notably as concerns the sampling, isolation into ex situ culture, and metabolic optimization of extremophile microorganisms. In addition to contributing to novel drug discovery, the project will generate fundamental knowledge to advance our understanding of the ecology and evolution of microbial diversity in these extreme environments, which like all other ecosystem compartments are subject to perturbation by ongoing climate change. All resources generated during the project which are not of immediate commercial interest will be made available to the scientific community via the public culture collections and databases hosted by project partners.