Final Report Summary - MARBIOTEC*EU-CN* (European-Chinese Research Staff Exchange Cluster on Marine Biotechnology)
Marine biotechnology has become a field of research of increasing economic importance worldwide. Many new products or product candidates to be used as pharmaceuticals, agrochemicals, food ingredients or cosmetics are of marine origin. One main reason for the rapid development of marine biotechnology is the tremendous genetic richness of the oceans providing a nearly inexhaustible source for novel secondary metabolites, biopolymers, enzymes/proteins, or new materials which are of interest for biomedicine, (nano)technology or other applications. More recently, marine products from unexplored or not sufficiently explored marine environments such as deep sea vents, manganese nodules or seamount crusts have attracted special attention. Even enzymes that are capable of forming inorganic materials have been isolated from a marine organism. Silicatein, a sponge protein, is the first enzyme found to catalyze the formation of inorganic silica. The fascinating ability of many marine organisms, such as sponges, to form a great variety of hierarchically structured inorganic skeletons over various length scales, from nano to macro, has raised the interest not only of biochemists and cell biologists but also of material scientists. Using marine organisms as a biomimetic model and their proteins/enzymes as a tool for the fabrication of novel nano-composite materials, marine biotechnology has started to become an innovative force even in micro- and optoelectronics. Moreover, marine organisms are a huge source for the discovery of novel lead compounds with a high potential to become a drug for therapy of human diseases. Therefore, “blue biotechnology” has been included in the priority programmes of many national and international funding organizations, including the European Union and China.
This multidisciplinary International Research Staff Exchange Scheme MarBioTec*EU-CN* was based on three institutions in Europe and four institutions in China, with outstanding groups in the areas of marine biotechnology, marine drug discovery and marine biominerals / nanotechnology. The objective of this project was the establishment of a joint exchange programme of staff between the participating institutions, allowing an effective transfer of knowledge and training of both early-stage researchers and experienced researchers. This project turned out to be of great benefit for participating institutions on both sides.
The Highlights of research and the industrially exploitable Products that resulted from this project can be summarized as follows.
The Highlights were, among others, the elucidation of the acquisition of structure-guiding and structure-forming properties of silicatein during maturation from pro-silicatein to silicatein, the demonstration that the silicatein pro-peptide controls the folding and function of the mature protein, the first description of the process of syneresis occurring after the silicatein-mediated polycondensation reaction during spicule formation, the discovery of the silicatein interactors, silintaphin-1 and silintaphin-2, and the demonstration that a synthetic peptide spanning the Glu/Asp rich region of silintaphin-2 significantly increases the silica polycondensation reaction, the development of a new scheme for the catalytic mechanism of silicatein, the elucidation of the cellular interplay that controls the morphogenetic processes during spiculogenesis, the description of a “nervous”-like signal transduction system in sponges that involves a luciferase-like protein (light source), the spicular system (optical waveguide) and a cryptochrome (photosensor), the generation of biomimetic optical fibres by micro-contact printing of silicatein on surfaces followed by enzymatic silica polycondensation, the bioinspired fabrication of biosilica-based bone-substitution materials, the development of novel biopolymer-based materials for sealing of teeth and protection against the caries, the demonstration that allylamine based plasma polymerized coatings can promote the attachment, spreading and in turn proliferation of human adipose-derive stem cells (hMSCs), the finding that the surface chemical gradient affects the differentiation of hMSCs via ERK1/2 signaling pathway, the result that the uptake of silver nanoparticles does not influence the osteogenic differentiation of hMSCs, giving a positive reference for the application of Ag NPs in bone tissue engineering, the demonstration that silver nanoparticles do not influence adipogenic differentiation of hMSCs, the preparation of TiO2-silicate hierarchical coatings on titanium surface for biomedical applications, the preparation of a novel titania/calcium silicate hydrate bi-layer coatings with hierarchical surface topography on titanium substrate through micro-arc oxidation and subsequent hydrothermal treatment, the demonstration of an enhanced fibronectin adsorption and initial MG-63 cell attachment on the novel titania/calcium silicate hydrate hierarchical coating on titanium, the understanding of biogenic origin of polymetallic nodules, the demonstration that coccoliths act as bio-seeds in biogenic ferromanganese crust formation, the development of methodologies for culturing marine invertebrate cells from molluscs and from scleractinian corals developed, the characterization of the microstructure and trace element composition of the calcitic biomineral in the giant tetractine spicules of a calcisponge, the demonstration that the impaired expression of the gene encoding for the carbonic anhydrase from a plant growing in Chinese Karst areas at higher pH can be counteracted both by addition of bicarbonate and inorganic polyphosphate which normalizes the increased pH in the vacuoles of the growing plants, the design of new strategies for biotechnological enrichment as well as for the removal of metals from marine environments, the isolation of a new indole alkaloid from a sponge-associated Streptomyces sp., the isolation of a novel bisabolene sesquiterpene dimer from a South China Sea sponge, the isolation of a library of brominated polyunsaturated lipids with inhibitory activity against pancreatic lipase from the sponge Xestospongia testudinaria and the determination of the structure-activity relationships of these compounds, the discovery of five new polyketide antimalarial endoperoxides from the sponge Plakortis simplex and the generation of a 3D pharmacophoric model, the identification of a new phosphorylated polyhydroxy polyketide from the ascidian Sidnyum elegans that acts as a potent protein tyrosine phosphatase 1B (PTP1B) inhibitor and also shows significant cytotoxicity against human cancer cells, the isolation of an unprecedented diterpenoid was isolated from Hainan soft coral Sarcophyton trocheliophorum Marenzeller as a PTP1B inhibitor, and the discovery of many new and bioactive steroids and terpenoids from Hainan soft corals, sponges, or mangroves.
The Products resulting from this project that can be offered are: (i) Printing technology of bioinspired optical fibres containing silicatein or silicatein mutants for enzymatic silica production (target group: optical industry, biomedical sensors, medical product industry) (contact: UMC); (ii) Novel biocompatible and biodegradable bone-substitution materials, based on biosilica, and technology for the production of 3D scaffolds of these materials (target group: hospitals, medical product industry) (contact: UMC); (iii) Technology to prepare protective coatings of teeth based on novel biopolymer-based materials (sealing of teeth; prevention of hypersensitivity; caries prophylaxis) (target group: dentists, medical product industry) (contact: UMC); (iv) Allylamine based plasma polymerized coatings to promote attachment, spreading and proliferation of human adipose-derive stem cells (target group: medical product industry) (contact: THU); (v) Titania/calcium silicate hydrate bi-layer coatings on titanium substrate produced by micro-arc oxidation and hydrothermal treatment (target group: medical product industry) (contact: THU); (vi) Methodologies for culturing marine invertebrate cells from molluscs and scleractinian corals (contact: MNHN, THU); (vii) Activators of expression of carbonic anhydrase gene in Karst plants (polyphosphates) (target group: water quality in Karst regions, environmental restoration, agricultural industry) (contact: UMC); (viii) Methods for biotechnological enrichment as well as for the removal of metals from marine environments (contact: UMC); (ix) Brominated polyunsaturated lipids acting as inhibitors of pancreatic lipase (target group: pharmaceutical industry) (contact: UNINA, SIMM-CAS); (x) New polyketide antimalarial endoperoxides (target group: pharmaceutical industry) (contact: UNINA); (xi) Novel protein tyrosine phosphatase 1B (PTP1B) inhibitors of potential biomedical interest (target group: pharmaceutical industry) (contact: SIMM-CAS).
There is a huge potential in the field of marine biotechnology and nano(bio)technology in China, which will also be of benefit for the European Research Area. This IRSES project helped to improve the development of marine biotechnology industry both in Europe and in China. It contributed to a durable integration of the research capacities in the multidisciplinary field of marine biotechnology between the countries on both sides.
This multidisciplinary International Research Staff Exchange Scheme MarBioTec*EU-CN* was based on three institutions in Europe and four institutions in China, with outstanding groups in the areas of marine biotechnology, marine drug discovery and marine biominerals / nanotechnology. The objective of this project was the establishment of a joint exchange programme of staff between the participating institutions, allowing an effective transfer of knowledge and training of both early-stage researchers and experienced researchers. This project turned out to be of great benefit for participating institutions on both sides.
The Highlights of research and the industrially exploitable Products that resulted from this project can be summarized as follows.
The Highlights were, among others, the elucidation of the acquisition of structure-guiding and structure-forming properties of silicatein during maturation from pro-silicatein to silicatein, the demonstration that the silicatein pro-peptide controls the folding and function of the mature protein, the first description of the process of syneresis occurring after the silicatein-mediated polycondensation reaction during spicule formation, the discovery of the silicatein interactors, silintaphin-1 and silintaphin-2, and the demonstration that a synthetic peptide spanning the Glu/Asp rich region of silintaphin-2 significantly increases the silica polycondensation reaction, the development of a new scheme for the catalytic mechanism of silicatein, the elucidation of the cellular interplay that controls the morphogenetic processes during spiculogenesis, the description of a “nervous”-like signal transduction system in sponges that involves a luciferase-like protein (light source), the spicular system (optical waveguide) and a cryptochrome (photosensor), the generation of biomimetic optical fibres by micro-contact printing of silicatein on surfaces followed by enzymatic silica polycondensation, the bioinspired fabrication of biosilica-based bone-substitution materials, the development of novel biopolymer-based materials for sealing of teeth and protection against the caries, the demonstration that allylamine based plasma polymerized coatings can promote the attachment, spreading and in turn proliferation of human adipose-derive stem cells (hMSCs), the finding that the surface chemical gradient affects the differentiation of hMSCs via ERK1/2 signaling pathway, the result that the uptake of silver nanoparticles does not influence the osteogenic differentiation of hMSCs, giving a positive reference for the application of Ag NPs in bone tissue engineering, the demonstration that silver nanoparticles do not influence adipogenic differentiation of hMSCs, the preparation of TiO2-silicate hierarchical coatings on titanium surface for biomedical applications, the preparation of a novel titania/calcium silicate hydrate bi-layer coatings with hierarchical surface topography on titanium substrate through micro-arc oxidation and subsequent hydrothermal treatment, the demonstration of an enhanced fibronectin adsorption and initial MG-63 cell attachment on the novel titania/calcium silicate hydrate hierarchical coating on titanium, the understanding of biogenic origin of polymetallic nodules, the demonstration that coccoliths act as bio-seeds in biogenic ferromanganese crust formation, the development of methodologies for culturing marine invertebrate cells from molluscs and from scleractinian corals developed, the characterization of the microstructure and trace element composition of the calcitic biomineral in the giant tetractine spicules of a calcisponge, the demonstration that the impaired expression of the gene encoding for the carbonic anhydrase from a plant growing in Chinese Karst areas at higher pH can be counteracted both by addition of bicarbonate and inorganic polyphosphate which normalizes the increased pH in the vacuoles of the growing plants, the design of new strategies for biotechnological enrichment as well as for the removal of metals from marine environments, the isolation of a new indole alkaloid from a sponge-associated Streptomyces sp., the isolation of a novel bisabolene sesquiterpene dimer from a South China Sea sponge, the isolation of a library of brominated polyunsaturated lipids with inhibitory activity against pancreatic lipase from the sponge Xestospongia testudinaria and the determination of the structure-activity relationships of these compounds, the discovery of five new polyketide antimalarial endoperoxides from the sponge Plakortis simplex and the generation of a 3D pharmacophoric model, the identification of a new phosphorylated polyhydroxy polyketide from the ascidian Sidnyum elegans that acts as a potent protein tyrosine phosphatase 1B (PTP1B) inhibitor and also shows significant cytotoxicity against human cancer cells, the isolation of an unprecedented diterpenoid was isolated from Hainan soft coral Sarcophyton trocheliophorum Marenzeller as a PTP1B inhibitor, and the discovery of many new and bioactive steroids and terpenoids from Hainan soft corals, sponges, or mangroves.
The Products resulting from this project that can be offered are: (i) Printing technology of bioinspired optical fibres containing silicatein or silicatein mutants for enzymatic silica production (target group: optical industry, biomedical sensors, medical product industry) (contact: UMC); (ii) Novel biocompatible and biodegradable bone-substitution materials, based on biosilica, and technology for the production of 3D scaffolds of these materials (target group: hospitals, medical product industry) (contact: UMC); (iii) Technology to prepare protective coatings of teeth based on novel biopolymer-based materials (sealing of teeth; prevention of hypersensitivity; caries prophylaxis) (target group: dentists, medical product industry) (contact: UMC); (iv) Allylamine based plasma polymerized coatings to promote attachment, spreading and proliferation of human adipose-derive stem cells (target group: medical product industry) (contact: THU); (v) Titania/calcium silicate hydrate bi-layer coatings on titanium substrate produced by micro-arc oxidation and hydrothermal treatment (target group: medical product industry) (contact: THU); (vi) Methodologies for culturing marine invertebrate cells from molluscs and scleractinian corals (contact: MNHN, THU); (vii) Activators of expression of carbonic anhydrase gene in Karst plants (polyphosphates) (target group: water quality in Karst regions, environmental restoration, agricultural industry) (contact: UMC); (viii) Methods for biotechnological enrichment as well as for the removal of metals from marine environments (contact: UMC); (ix) Brominated polyunsaturated lipids acting as inhibitors of pancreatic lipase (target group: pharmaceutical industry) (contact: UNINA, SIMM-CAS); (x) New polyketide antimalarial endoperoxides (target group: pharmaceutical industry) (contact: UNINA); (xi) Novel protein tyrosine phosphatase 1B (PTP1B) inhibitors of potential biomedical interest (target group: pharmaceutical industry) (contact: SIMM-CAS).
There is a huge potential in the field of marine biotechnology and nano(bio)technology in China, which will also be of benefit for the European Research Area. This IRSES project helped to improve the development of marine biotechnology industry both in Europe and in China. It contributed to a durable integration of the research capacities in the multidisciplinary field of marine biotechnology between the countries on both sides.