Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MarPipe (Improving the flow in the pipeline of the next generation of marine biodiscovery scientists)

Teaser

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...

Summary

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 are 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.

Work performed

MarPipe intends 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 is 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. The MarPipe consortium encompasses academic institutions, research centres, and SMEs, all with proven experience in higher education and training, and endowed with state-of-the art scientific and technical expertise and infrastructures.

Final results

From the beginning of the project, the following papers have been published:

- M. Pérez-Bonilla, D. Oves-Costales, M. de la Cruz, M. Kokkini, J. Martín, F. Vicente, O. Genilloud, F. Reyes. Phocoenamicins B and C, new Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp. Mar. Drugs, 2018, 16, 95.

- Parrot D., Papazian S., Foil D., Tasdemir D. Imaging the unimaginable: Desorption Electrospray Ionization - Imaging Mass Spectrometry (DESI-IMS) in natural product research. Planta Medica, 2018, 84, 584-593.

- Martínez Andrade, K.A.; Lauritano, C.; Romano, G.; Ianora, A. ‘’Marine Microalgae with Anti-Cancer Properties’’. Marine Drugs 2018, 16, 165.

- Romano, S., Jackson, S.A., Patry, S. and Dobson, A.W.D. (2018). Extending the “one strain many compounds” (OSMAC) principle to marine microorganisms. Marine Drugs 16(7). Pii:E244; doi:10.3390/md16070244

Website & more info

More info: http://www.marpipe.eu.