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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DOC (Dark Ocean Cosmeceuticals -DOC-: The Cosmetical and Pharmaceutical Potential of Marine Dissolved Organic Matter)

Teaser

Summary

Based on the discovery of novel ways to counteract the side effects of population ageing and the emergence of new diseases and multiresistant microbes, the overall goal of DOC was the proof of principle of the cosmetical and pharmaceutical potential of one of the largest reservoirs of organic material on Earth: the recalcitrant marine dissolved organic matter (RDOM) pool, and lay the ground for a more extensive exploration in the future. Unlike the largest exploited organic carbon pools, petroleum and coal, the potential of this RDOM pool has never been explored until Dr. CatalÃ¡â€™s MSCA-IF.

The overarching hypothesis of this proposal was that marine DOM contains bioactive components with cosmeceutical potential. This hypothesis was broken down into the following working hypotheses (H):
H1. An operationally defined fraction of RDOM (in terms of molecular size and polarity) is bioactive.
H2. These bioactive properties can be related to certain molecular features.
H3. Contrasting bioactive products are found in the dark ocean, surface ocean and marine sediments DOM.
H4. The bioactive DOM fractions are applicable for cosmeceutical purposes.

This MSCA-IF has demonstrated that marine RDOM contains bioactive components with biotechnological potential. It was also confirmed that operationally defined fractions of RDOM (in terms of polarity) are bioactive (Hypothesis 1), that these bioactive properties can be related to certain molecular features (Hypothesis 2), and that contrasting bioactive products exist in the dark ocean, surface ocean and marine sediments DOM (Hypothesis 3).

Work performed

First, the water-column and sediment porewater RDOM samples were collected and extracted. In order to reduce the molecular complexity, the samples were fractionated by polarity by using different solvents.

Non-fractionated DOM pools and fractions were analyzed for bioactive potential. The first results showed antioxidant activities and phenolic content much higher of what is commonly found in macroalgae and microalgae with cosmeceutical purposes, in vegetables, in fruits, in honey, and in the same magnitude as propolis. A surprising finding was the excellent solar protection factor index (SPF), especially of the sediment-derived DOM, which showed SPF/UVASPF ratios very closed to the ideal sunscreen.
Regarding the immunoactivity, the pro-inflammatory cytokine TNF-Î± was the most expressed. The pro-inflammatory IL-2, GM-CSF and IFN-Î³, and the anti-inflammatory IL-4 were only expressed in some of the fractions, whereas IL-13, IL-10, IL-5 and IL-12 (p70) were not expressed.
For all these tests, the sediment porewater DOM was the most biologically active, presumably related to its elevated sulfur content. In some cases, a magnification of the bioactive potential of DOM was observed after fractionating the crude material, indicating a molecular-dependent bioactive response.

Thanks to an EMBRIC transnational access program (http://www.embric.eu), Dr. CatalÃ¡ measured the anti-tumoral and anti-microbial activity of RDOM. The anti-tumoral activity with human prostate cancer cells (PC3), with its healthy counterpart for comparison, was measured. Whereas some samples did not show a cytotoxic effect on both human cells, some other showed antiproliferative effect on normal cells or/and tumor cells. The anti-microbial testing was evaluated with seven different multidrug-resistant strains from the Collection of Institut Pasteur. Slight anti-microbial activities were found in the strains Staphylococcus aureus aureus and Klebsiella pneumoniae pneumoniae.
Since no clear patterns were observed in any of the two assays, there is a need for other types of pharmaceutical tests adapted to complex natural mixtures.

Together with the bioactivity tests, the samples molecular composition was elucidated. The results showed how the porewater samples are molecularly different regarding the water column samples. Most of the formulas present in the porewater are exclusive and they are not present in the other two groups. In addition, the fractionation by polarity was very successful in separating the RDOM in different molecular groups.

Due to initial complications, the publication of scientific papers was not achieved yet. Instead, a first publication linking antioxidant activity and phenolic content with the molecular features is in preparation, together with a second publication on the immunoactivity.

Throughout the project, Dr. CatalÃ¡ has given lectures to a variety of audiences. In the host and all collaborating institutions, she has given lectures presenting her project. She has presented her work at the 2018 Ocean Sciences Meeting conference (Portland, February 2018). In January 2019, she gave a lecture at the microbiology seminar at the Institut Pasteur (Paris) and she presented her results in the final EMBRIC meeting in early 2019. Two press releases have been published at Oldenburg University, one explaining what her research consisted of (https://uol.de/news-detail/die-schatztruhe-des-ozeans-oeffnen-2153/) and the other concluding the results obtained and future perspectives (https://www.presse.uni-oldenburg.de/mit/2019/211.html).

Final results

Although the collaborating institutions allowed Dr. CatalÃ¡ to present the first hints of RDOM bioactive potential, this first exploration is still in an early stage and further in-depth investigation together with specialists on the topic is crucially required. To fulfill this aim, she got recently a â€œStart-up funding for junior research groups, Programmhaushalt Forschung (PH-F)â€ of Oldenburg University (Germany), with a consequent perspective of achieving a European Research Council (ERC) Starting Research Grant in the next two years.

The two added institutions to her new project, the Stazione Zoologica Anton Dohrn of Napoli (SZN, Italy) and the Institut Pasteur (Paris, France), will bring new insights in the bioprospection for marine novel complex natural mixtures. Contrary to the specific measures Dr. CatalÃ¡ did during her MSCA-IF, in her new project, she will deepen in the evaluation of the DOM bioactive potential. The Marine Biotechnology specialist group in Naples will guide her on the screening of the biotechnological potential of DOM samples. By collaborating with the Institute Pasteur, the medical and pharmaceutical pipeline will be much more present, she will be able to work directly with bacterial strains that cause illnesses that are incurable today and she will get access to high-throughput and cell-based phenotypic screening in order to circumvent the difficulty encountered and the limitations of techniques based on individual assays.

In her new project, she will also work directly with the interested companies to proceed with the commercialization of cosmeceutical and nutraceutical products, as well as to continue with the following trials within the world of pharmaceuticals, which requires much more time. Although her main pipeline is pharmaceuticals, she finds the fields of nutraceuticals and cosmeceuticals also of great interest and with great accessibility to the society.

Dr. CatalÃ¡Â´s aspiration keeps lying in the opening of a multidisciplinary research line where, combining the areas of biogeochemistry, natural products research and biotechnology, she can access to the bioactive potential of the RDOM, identifying those molecular groups of greater impact to ultimately forward them to the society.