Periodic Reporting for period 2 - MarPipe (Improving the flow in the pipeline of the next generation of marine biodiscovery scientists)
Reporting period: 2018-11-01 to 2021-04-30
Marine organisms possess the capacity to produce a variety of unique and biologically potent natural products. Novel molecules might display their activity through new mechanisms of action and therefore could be used to treat human diseases and enhance the quality of life, especially as regards ageing of the population. According to the WHO by 2040 the global population aged 65 and over is estimated to reach 1.3 billion and consequently the prevalence of age-related diseases (e.g. cardiovascular diseases, metabolic disorders, neurodegenerative diseases, cancer and infectious diseases) will increase dramatically. Despite unprecedented interest in marine natural products (MNP) as potential therapeutic agents for a variety of human age-related diseases, relatively few MNP have reached the late stages of the clinical development and the market. To fully exploit the marine biological resources, new strategies in the marine biodiscovery pipeline are needed to overcome existing bottlenecks and ensure the production of high value biomolecules.
The specific scientific objectives of MarPipe were therefore to:
1. Further develop hits already identified in 10 strains by MarPipe partners in ongoing EU projects (e.g. PharmaSea, MaCuMBA), in the anti-infective and anticancer fields (hereafter called “Magnificent 10”).
2. Analyse microorganisms that are currently uncultivable and improve methods of their cultivation and co-cultivation in order to optimize production of bioactives compounds. Samples will be provided by the Eurofleet2- Pharmadeep cruise in December 2015 in sub Antarctic deep-sea trenches (Drake Passage, 5000 m).
3. Apply functional bioassays by using metabolic engineering for the discovery of molecular pathways, or apply OSMAC and co-cultivation techniques to awaken silent biosynthetic pathways.
4. Apply sophisticated analytical methods and develop new protocols for the stimulation (of biosynthesis), extraction, isolation, purification and enrichment of biomolecules.
5. Apply medicinal chemistry approaches to optimize the efficacy of target molecules.
6. Scale-up production processes through flexible bioreactor technologies.
7. Address legal and policy constraints in the drug discovery pipeline.
8. Develop innovation and business strategies for drug biodiscovery.
The specific scientific objectives of MarPipe were therefore to:
1. Further develop hits already identified in 10 strains by MarPipe partners in ongoing EU projects (e.g. PharmaSea, MaCuMBA), in the anti-infective and anticancer fields (hereafter called “Magnificent 10”).
2. Analyse microorganisms that are currently uncultivable and improve methods of their cultivation and co-cultivation in order to optimize production of bioactives compounds. Samples will be provided by the Eurofleet2- Pharmadeep cruise in December 2015 in sub Antarctic deep-sea trenches (Drake Passage, 5000 m).
3. Apply functional bioassays by using metabolic engineering for the discovery of molecular pathways, or apply OSMAC and co-cultivation techniques to awaken silent biosynthetic pathways.
4. Apply sophisticated analytical methods and develop new protocols for the stimulation (of biosynthesis), extraction, isolation, purification and enrichment of biomolecules.
5. Apply medicinal chemistry approaches to optimize the efficacy of target molecules.
6. Scale-up production processes through flexible bioreactor technologies.
7. Address legal and policy constraints in the drug discovery pipeline.
8. Develop innovation and business strategies for drug biodiscovery.
MarPipe intended to improve the feasibility of marine natural products through: the identification of eco-friendly, renewable marine bioresources, innovative screening protocols; the isolation, structural elucidation of new molecules and dereplication procedures as well as improvement in biomass production and scale-up processes. To this end, the project encompasses a wide variety of disease targets including infections, cancer.
MarPipe was training 11 PhD students in a programme including training-by-research, joint courses of technical, scientific, and transferrable skills, active participation to public scientific events, and an intense inter-sectoral networking exchange plan.
During their studies, MarPipe ’s fellows and mentors were very active in communication and outreach, having already published 23 scientific papers, and participated to over 90 science communication events targeting the scientific community, the general public and industrial and regulatory stakeholders.
MarPipe was training 11 PhD students in a programme including training-by-research, joint courses of technical, scientific, and transferrable skills, active participation to public scientific events, and an intense inter-sectoral networking exchange plan.
During their studies, MarPipe ’s fellows and mentors were very active in communication and outreach, having already published 23 scientific papers, and participated to over 90 science communication events targeting the scientific community, the general public and industrial and regulatory stakeholders.
Papers published jointly by PIs and fellows:
1. Arianna Giusti, et al (2019). Safety Assessment of Compounds after In Vitro Metabolic Conversion Using Zebrafish Eleuthero Embryos. International Journal of Molecular Sciences, 20/7, 1712.
2. Martínez Andrade, K.A. et al (2018).‘’Marine Microalgae with Anti-Cancer Properties’’. Marine Drugs, 16, 165.
3. Parrot D., et al (2018). Imaging the unimaginable: Desorption Electrospray Ionization - Imaging Mass Spectrometry (DESI-IMS) in natural product research. Planta Medica, 84, 584-593.
4. M. Pérez-Bonilla, et al (2018). Phocoenamicins B and C, new Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp. Mar. Drugs, 16, 95.
5. Romano, S., et al (2018). Extending the “one strain many compounds” (OSMAC) principle to marine microorganisms. Marine Drugs 16(7). Pii:E244; doi:10.3390/md16070244.
6. Tortorella, E., et al (2018). Antibiotics from Deep-Sea Microorganisms: Current Discoveries and Perspectives. Marine Drugs, 16(10), p.355.
7. Gavriilidou, A.,et al (2020). Comparative genomic analysis of Flavobacteriaceae: insights into carbohydrate metabolism, gliding motility and secondary metabolite biosynthesis. BMC Genomics 21, 569.
8. Gavriilidou, A., et al (2021). Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria. Marine Drugs 19, 75.
9. Martínez, K.A. et al (2019). Amphidinol 22, a New Cytotoxic and Antifungal Amphidinol from the Dinoflagellate Amphidinium carterae. Mar. Drugs, 17, 385.
10. Collins, J.E. et al (2021). Strengthening a Global Network of Marine Biological Collections: Recommendations for Biodiversity Beyond National Jurisdiction. ICES Journal of Marine Science Volume 78, Issue 1, Pages 305–314.
11. Collins, J.E. et al (2020). Developing a Methodology to Balance Benefit-Sharing: Application in the Context of Biodiversity Beyond National Jurisdiction. Genetic Resources. Vol 1, N°1.
12. Collins, J.E. et al (2020). Stakeholder Perspectives on Access and Benefit-Sharing for Areas Beyond National Jurisdiction. Frontiers in Marine Science, 7, p.265.
13. Collins, J.E. et al (2020). Marine Bioresource Development-Stakeholder's Challenges, Implementable Actions and Business Models. Frontiers in Marine Science, 7, p.62.
14. Collins, J.E.,et al (2019). Inclusive innovation: Enhancing global participation in and benefit sharing linked to the utilization of marine genetic resources from areas beyond national jurisdiction. Marine Policy, 109, p.103696.
15. Rabone, M., et al 2019). Access to Marine Genetic Resources (MGR): raising awareness of best-practice through a new agreement for Biodiversity Beyond National Jurisdiction (BBNJ). Frontiers in Marine Science, 6, p.520.
16. Collins, J.E. et al (2018). Blue Biotechnology. Building Industries at Sea: 'Blue Growth' and the New Maritime Economy. River Publishers
17. Yannik K-H Schneider, et al (2019). Anti-Bacterial Effect and Cytotoxicity Assessment of Lipid 430 Isolated from Algibacter sp. Molecules, Nov 5;24(21):3991.
18. G A Vitale, et al. J Nat Prod, 2020 May 22;83(5):1495-1504. Epub 2020 Apr 10.
19. Lauritano C., et al (2020) First evidence of anticancer and antimicrobial activity in Mediterranean mesopelagic species. Scientific reports. 10, 4929.
20. Saide A, et al (2021). Unlocking the Health Potential of Microalgae as Sustainable Sources of Bioactive Compounds. Int. J. Mol. Sci. 22, 4383.
21. Yannik K-H Schneider. (2020). Bioactive secondary metabolites from bacteria. Natural products from marine and terrestrial bacteria, dereplication, isolation and investigation of bacterial secondary metabolites. PhD thesis.
22. Yannik Schneider, et al (2020). Bioactivity of Serratiochelin A, a Siderophore Isolated from a Co-Culture of Serratia sp. and Shewanella sp. Microorganisms. 14;8(7):1042.
23. Marlly Guarin, et al (2021). Spatiotemporal imaging and pharmacokinetic of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration. Scientific Reports. In press.
1. Arianna Giusti, et al (2019). Safety Assessment of Compounds after In Vitro Metabolic Conversion Using Zebrafish Eleuthero Embryos. International Journal of Molecular Sciences, 20/7, 1712.
2. Martínez Andrade, K.A. et al (2018).‘’Marine Microalgae with Anti-Cancer Properties’’. Marine Drugs, 16, 165.
3. Parrot D., et al (2018). Imaging the unimaginable: Desorption Electrospray Ionization - Imaging Mass Spectrometry (DESI-IMS) in natural product research. Planta Medica, 84, 584-593.
4. M. Pérez-Bonilla, et al (2018). Phocoenamicins B and C, new Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp. Mar. Drugs, 16, 95.
5. Romano, S., et al (2018). Extending the “one strain many compounds” (OSMAC) principle to marine microorganisms. Marine Drugs 16(7). Pii:E244; doi:10.3390/md16070244.
6. Tortorella, E., et al (2018). Antibiotics from Deep-Sea Microorganisms: Current Discoveries and Perspectives. Marine Drugs, 16(10), p.355.
7. Gavriilidou, A.,et al (2020). Comparative genomic analysis of Flavobacteriaceae: insights into carbohydrate metabolism, gliding motility and secondary metabolite biosynthesis. BMC Genomics 21, 569.
8. Gavriilidou, A., et al (2021). Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria. Marine Drugs 19, 75.
9. Martínez, K.A. et al (2019). Amphidinol 22, a New Cytotoxic and Antifungal Amphidinol from the Dinoflagellate Amphidinium carterae. Mar. Drugs, 17, 385.
10. Collins, J.E. et al (2021). Strengthening a Global Network of Marine Biological Collections: Recommendations for Biodiversity Beyond National Jurisdiction. ICES Journal of Marine Science Volume 78, Issue 1, Pages 305–314.
11. Collins, J.E. et al (2020). Developing a Methodology to Balance Benefit-Sharing: Application in the Context of Biodiversity Beyond National Jurisdiction. Genetic Resources. Vol 1, N°1.
12. Collins, J.E. et al (2020). Stakeholder Perspectives on Access and Benefit-Sharing for Areas Beyond National Jurisdiction. Frontiers in Marine Science, 7, p.265.
13. Collins, J.E. et al (2020). Marine Bioresource Development-Stakeholder's Challenges, Implementable Actions and Business Models. Frontiers in Marine Science, 7, p.62.
14. Collins, J.E.,et al (2019). Inclusive innovation: Enhancing global participation in and benefit sharing linked to the utilization of marine genetic resources from areas beyond national jurisdiction. Marine Policy, 109, p.103696.
15. Rabone, M., et al 2019). Access to Marine Genetic Resources (MGR): raising awareness of best-practice through a new agreement for Biodiversity Beyond National Jurisdiction (BBNJ). Frontiers in Marine Science, 6, p.520.
16. Collins, J.E. et al (2018). Blue Biotechnology. Building Industries at Sea: 'Blue Growth' and the New Maritime Economy. River Publishers
17. Yannik K-H Schneider, et al (2019). Anti-Bacterial Effect and Cytotoxicity Assessment of Lipid 430 Isolated from Algibacter sp. Molecules, Nov 5;24(21):3991.
18. G A Vitale, et al. J Nat Prod, 2020 May 22;83(5):1495-1504. Epub 2020 Apr 10.
19. Lauritano C., et al (2020) First evidence of anticancer and antimicrobial activity in Mediterranean mesopelagic species. Scientific reports. 10, 4929.
20. Saide A, et al (2021). Unlocking the Health Potential of Microalgae as Sustainable Sources of Bioactive Compounds. Int. J. Mol. Sci. 22, 4383.
21. Yannik K-H Schneider. (2020). Bioactive secondary metabolites from bacteria. Natural products from marine and terrestrial bacteria, dereplication, isolation and investigation of bacterial secondary metabolites. PhD thesis.
22. Yannik Schneider, et al (2020). Bioactivity of Serratiochelin A, a Siderophore Isolated from a Co-Culture of Serratia sp. and Shewanella sp. Microorganisms. 14;8(7):1042.
23. Marlly Guarin, et al (2021). Spatiotemporal imaging and pharmacokinetic of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration. Scientific Reports. In press.