Biofouling is the undesirable growth of living organisms (bacteria, algae, mollusks etc) on structures submerged in water which causes serious problems for the aquaculture and maritime industries. A number of physical and chemical technologies have been applied in antifouling paints (AF), the most effective of them being the use of tributyltin coatings. However, due to toxicity caused by tributyltin and heavy metals, in September 2008, the International Maritime Organization (IMO) banned the use of self-polishing tributyltin coatings and there is increasing opposition to the use of copper. Preventing the settlement of fouling organisms in a non-toxic manner would be the ideal solution. To this end, there has been a multitude of physical, chemical and biomimetic approaches. Likely, a successful method of AF will need to combine all methods. Over the past few years several marine metabolites were characterized for their eco-friendly antifouling potential. Among them, a very promising halogenated terpene, bromosphaerol from S. coronopifolius isolated by our group. Currently, the major hurdle of the use of marine metabolites is the limited available quantities. To address this limitation, our consortium will approach bromosphaerol biosynthesis in an interdisciplinary manner utilizing all available new tools in biotechnology, genomics, bioinformatics, biochemical and chemical analysis and in-vivo assays. In preliminary work, we have applied Next Generation Sequencing (NGS) to identify several thousand of expressed genes from S. coronopifolius including candidate terpenoid biosynthetic genes. In the current project we will expand the NGS approach in additional fresh material, analyze bioinformatically the expressed genes to quantify expression levels, isolate candidate biosynthetic genes, perform enzymatic analysis and metabolic modeling and flux analysis, reconstitute the biosynthetic pathway in heterologous species, refine the chemical analysis tools to identify compounds from tiny amounts of algal material and settlement-inhibition assays of barnacles.

Several recent major scandals have tarnished public confidence in the evaluation and monitoring system for high-risk medical technologies (HRMD). These situations and the "Implant files" investigation, which denounced the ease with which manufacturers can obtain the right to market medical devices in Europe, highlighted the weaknesses and flaws in the health control system for placing on the market and monitoring it, in particular for HRMD. The new European regulations (EU MDR 2017/745) will come into effect in spring 2020. This new regulation sets forth reinforced rules for the generation of clinical evidence, in particular for the HRMD (current class III and implantable devices) for which clinical investigation will be compulsory. This is a big challenge for European Health SMEs (some 25,000 companies, representing 95% of the MedTech sector in Europe) to maintain their competitiveness and innovation capacity, with limited internal resources; especially in clinical trial skills. On the other hand, patients and physicians would like to ensure that the knowledge on the innovation allows for safe and efficient use of the new product. HRMD have specific features compared to drugs, such as the long-term use with unknown interactions with the human body, the means of explanting and replacing implantable devices, the user's skills, the human-machine interfaces, the management of generated data flows, etc. These specificities require specific evaluation methodologies to generate better clinical evidence. The objective of the research program will be to develop and promote methodological approaches accepted by sponsors and recognized by the evaluators. These approaches include patient involvement, mixed hybrid methods, numerical modeling, AI & Big data mining and alternative statistical methodologies, adapted to the specificities of HRMD. The goal will be to propose a new HRMD evaluation and approval process based on robust methodological approaches to the clinical data needed for the different phases of the product's life, such as clinical proof of concept, usability, premarket approval compliance, high quality clinical evidence for reimbursement, and adequate post-marketing clinical follow-up. Operational objectives - to analyze the current situation of clinical evaluation of HRMD: strengths; weaknesses; duration; indicators and criteria...It will be done by carrying out surveys and a review of the currently used investigation designs, providing a hierarchy of these approaches, identifying gaps to be filled. - by utilizing use cases, and panels of experts, develop methodologies through data-reuse, deep learning of existing medical databases, and hybrid methods for designing clinical investigation studies. - test these new methodologies for the evaluation of innovative HRMD, in close collaboration with all the involved parties (patients, academics, clinical staff, sponsors, industrials) - after this testing phase, propose new methodological references for dealing with the HRMD evaluation methodology and propose recommendations for the choice of the most powerful ones allowing to obtain sufficient evidence in terms of efficiency and safety of the HRMD - validation and implementation of proposed new approaches in close collaboration with industrial, stakeholders, networks of experts, competent authorities, and European Commission. - training program for stakeholders involved in the clinical evaluation of HRMD about the new regulatory framework with regard to clinical evidence. Within the framework of the ANR-MRSEI project, we propose to set up a consortium on the basis of the members of two involved European organizations (ECRIN and EIT-Health) and INSERM (Tech4Health network), supplemented by partners from some organizations as Notified Bodies Assembly, European Patient Associations, European Network for Health Technology Assessment (EUnetHTA), Society of European scientists and Competent Authorities for Medical Devices (CAMD).