Final Report Summary - DYNANO (DYNAMIC INTERACTIVE NANOSYSTEMS) Summary description of the Project objective: The key and direct objective of DYNANO was to provide training with a deep knowledge and expertise on Dynamic Interactive Nanosystems for biomedical and biotechnological applications on the basis of the existing scientific and technological areas: dynamic chemistry / glycosciences / biology / nanosciences. This multidisciplinary approach brings together scientists and key private industry players with complementary backgrounds, as essential developmental pillars.Scientific Progress: The DYNANO scientific progress is related to important collaborative achievements. 41 and 113 individual scientific publications, 14 publications by ESR/ER were published in high impact journals (Nature Comm, Angew. Chemie, JACS, Chem. Commun, etc. Also 223 lectures have been reported by the DYNANO senior researchers and ESR/ER during the 4 years. The DYNANO contributions to this field have been recently highlighted by the coordination of 3 successive dedicated joint actions, involving a strong contribution of the network partners and shedding light on the interest of the scientific community for the scientific fields structuring the DYNANO scientific platform: • Book Constitutional Dynamic Chemistry, Topics in Current Chemistry, M Barboiu Editor, Springer Verlag, 2012. http://www.springer.com/us/book/9783642283437• Special issue of coordinated by J.M. Lehn and M. Barboiu, Israel J. Chem. 2013, 53(1-2) Constitutional Dynamic Systems. http://onlinelibrary.wiley.com/doi/10.1002/ijch.v53.1/2/issuetoc• the RSC Special Issue of Organic and Bimolecular Chemistry 2015, Multivalent Biomolecular Recognition -22 papers, coordinated by S. Vincent, O. Ramstrom and M. Barboiu and containing papers of the DYNANO network partners and contributions of external scientists. http://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=ob&themeid=2f58d7eb-118c-4500-870f-7161ddb4a26eA number of about 51 oral communications and posters (excepting those of DYNANO meetings) have been already presented by our students at different international meetings like: ACS, NAMS, ISCC, IMEV, etc. The scientific impact of the network is challenging to estimate, but the DYNANO area have met considerable appreciation at conferences and symposia. A multitude of presentations from Senior scientists and YRs have been performed during the period, with considerable impact being made. A number of breakthroughs published in high impact journal have been made during the period: • Increased comprehension of molecular biointeractions. Gathering scientists at all the interfaces of different sciences has provided significant advances in the comprehension of molecular recognition and hierarchical self-assembly at the various scales. The main topics are related to the study of ligand/receptor interaction, mainly focused on sugars as ligand and Proteins or Enzymes as receptors. Seminal papers published in Acc. Chem. Res, Angew Chemie, Chemistry an European Journal.• Self-assembled water/ion channels: of highly applied research importance: production of ultrapure water, vaccines, etc. (collaboration IEM-ICS-UDS, IEM-External partner) seminal papers published in Nature. Chem, Acc. Chem Res. Angew Chemie, JACS.• Development and application of an entirely new dynamic covalent reaction: Native Chemical Ligation for the dynamic exchange of peptide bonds in physiological conditions. A seminal paper was published in the JACS, together with an approved patent. (collaboration ICS-UNamur) .• Functional triarilamine systems: a) the first dynamic self-assembly of triarylamine macrocyle; b) the first insertion of dynamic supramolecular structures in silica nanopores to access electrodes and biocathodes and c) the first use of self-assembled triarylamine derivatives in phospholipid bilayers to transport ions and water across membranes. (collaboration IEM-ICS-UDS)• Novel multivalent platforms: glycofullerenes, nanoparticles (NPs), Glyco-borromean rings, Dynamic Constitutional Frameworks. Seminal papers published in Chem. Rev., Angew Chemie, Chemistry. Progress has been made in the identification and generation of novel dynamic platforms for multivalent recognition and enzyme inhybition. These new breakthroughs have created considerable scientific impact. (collaboration KTH-UNamur-CSIC, KTH-UFirenze, IEM-ICS etc.)• Controlled selection and separation processes. Dynamic membrane systems can be developed for controlled selection of exosomes in direct collaborative academic/industry interactions. Combined Academic labs-Industry strategies have been effectively shared (collaboration IEM-SE-GVS, ATTANA-SE-CSIC, SOLVAY-ICS, etc.) for the elaboration of as soon merged marketable membranes for blood exosomes filtration. Development of a novel filtration system for the Leucodepletion of platelet concentrates. (GVS)• Microarrays. New advances in the field of microarrays have been made In the glycosciences, glycol-microarray systems of this type may form a range of new applications. These developments may generate extrapolations to diagnostics etc (collaboration SE-UNamur-ATTANA-CSIC). • Identification and characterization of target proteins and ligands. New molecules inhibiting therapeutically relevant targets have been discovered. Identification for the first time of the human epidermal growth factor receptor (EGFR) subjected to O-GlcNAcylation in carcinoma cells. These findings have potential applications for the treatment of cancer and infectious diseases. Seminal papers published in Org. Biomol; Chem, Plos one.• New biosensor applications. A number of new biosensor applications have been developed. These will facilitate the analysis of complex protein-carbohydrate of cell-metabolites interactions (collaboration IEM-ICB-ATTANA). Training: The DYNANO network has been composed to encompass all expertises in the highly interdisciplinary and intersectorial areas. All researchers have experienced training in all disciplines, with special emphasis on the training given by the main host, where the participating partners hold thorough expertise in their respective fields. The training has been made during external meetings and workshops. We started our project with the organization of the Open Problems in Systems Chemistry Symposium that brought together scientists representing all research domains of the Systems Chemistry: Chemistry, Life Sciences, Chemical Biology, Biophysics. Participants of Labex Chemisyst (Pole Balard, Montpellier), Labex Systems Chemistry (University of Strasbourg) and European ITN DYNANO, had the opportunity of meeting across the boundaries of different disciplines and the opportunity of finding a common language to discuss scientific items from various perspectives. Then, the Ist DYNANO workshop in Montecatini Terme dealt with many different topics, ranging from Dynamic Constitutional Chemistry (N. Giuseppone) and Dynamic Glycochemistry (J.J. Barbero and S. Vincent) to a presentation on employment skills-Horizon 2020 (Gilbert Rios). The 2nd DYNANO workshop in Budapest has been successfully organized on March 27th-29th. The workshop mainly focused on biological aspects of the research and training program, answering previous requests of the ESR/ERs. In addition, a visit to the laboratories of the Department of Genetics at Semmelweis University. The 3rd DYNANO workshop in Madrid has been organized at the Biological Research Centre (CIB) of CSIC in collaboration with the ITN GLYCOPHARM, as a 3-day joint Summer School. Among other activities, a special session was devoted to Women in Science, with one lecture analysing the progress of women in the scientific career, the Curie family presented as exceptional example of dual career couple, and a second lecture giving an inspiring example on the potential impact of science on society and on how putting knowledge into action can help to change the world. The summer school also included a visit to several CIB labs and a very constructive open discussion session with Prof. Jean-Marie Lehn (Nobel Prize in Chemistry 1987), right after his closing lecture. Training activities continued with a Management Lecture on Higher Education (Prof. Joao Crespo) and a final Brainstorming Session, as this has proved to be very useful for fostering and strengthening collaborations among young and senior researchers in the network. The 4th DYNANO Workshop has been held on April 2014 in Namur, Belgium. It will be organized by the the University of Namur in collaboration with MultiGlycoNano Multivalent Glycosystems for Nanoscience COST Action CM1102. The 5th DYNANO’s QCM Training Course and Meeting has been held during 01-06 September 2014 in Stockholm, Sweden The first three days were dedicated to the QCM course, delivered by Attana at KTH. Two external speakers were invited for the complementary courses which focused on entrepreneurship and career management: B. O. Nilsson, CEO at the Royal Swedish Academy of Engineering Sciences (IVA) and Rémi Caraballo, a former ESR at KTH of the previous ITN DYNAMIC and currently a research engineer chief at Umeå University. He gave the ESR/ERs a glimpse of the various career options that the ITN can offer. The 6th DYNANO Network Meeting was organized 15-18 April 2015 at ICB, Bucharest. A special scientific lecture was delivered by O. Popescu, member of the Romanian Academy. The Director of the Romanian State Office for Inventions and Trademarks, Dr. B. Ionescu, gave a complementary course on patent and IPR issues. The 7th DYNANO's Meeting was organized joined with the 10th International Symposium on Macrocyclic and Supramolecular Chemistry organized by UDS-Strasbourg in June 2015. Prof. J.-M. Lehn and M. Barboiu were speakers at this international conference and 6 ESRs and ERS from the DYNANO presented their research results during the poster sessions. DYNANO's final meeting was organized in Montpellier, 27-28 July 2015, joint with the Labex Chemisyst (Montpellier, Fr.) - Labex CSC Strasbourg (Fr.) and Pole Balard (Montpellier, Fr.). The conference was organized by the coordinator, Dr. Mihai BARBOIU (CNRS – IEM). The conference had a multidisciplinary approach: from chemistry to biology, materials and physics, giving raise to new research views of identifying and solving problems. Societal and ethical impact: DYNANO project has been of fundamental nature, leading to new knowledge in the areas of dynamic chemistry, glycochemistry, analytical chemistry and molecular recognition of carbohydrate-binding proteins. Substantial progress in the domain has been made, leading to a range of important results that will be used in environmental sciences, biotechnology and biomedicine. The new nanoplatforms developed during the project will thus serve as a base for future development towards new applications in water desalination drug-delivery, biosensing, imaging, cancer theranostics, and for combating bacterial and viral infections. 1. Environmental solutions for water purification: Our studies led to artificial water channels which could be used for bio-inspired desalination processes that could use the non-existing all-made artificial synthetic materials that mimic the mechanisms of natural desalinators. Therefore our first results aimed to explore the naturally-evolved desalination pathways and assess the possibilities of using them as the basis for ‘engineered’ desalination processes of enhanced performance. As far as the production of ultrapure water is concerned, the hallmark of ambitious concerned applications is mostly related to desalination.2. Biotechnology, Medicine and Health A. Microarrays for diagnostic: In the short-term, it is expected that the new microarrays, as well as the scientific results obtained in this project, will be mainly exploited by the scientific community. For raising awareness about the results and illustrating how they can be transferred and, when necessary, adapted to other specific research needs, extensive diffusion via scientific publications and presentations at seminars, workshops, scientific meetings, conferences, etc, will be undertaken. B. Novel filtration system for the Leucodepletion of platelet concentrates in blood transfusion: Leukodepletion filters are an important tool in blood transfusion centers to prevent transfer of pathogens from blood donors to patients. GVS SPA is active in this market area and intends to exploit the new filter. The commercialization of the filter is expected to increase the turnover related to this type of filters (blood transfusion filters) of about 15%. C. Extracellular vesicles for therapeutics: There is an emerging trend in the extracellular vesicle field towards therapeutic applications. When scalable production of extracellular vesicle preparations for therapeutics applications is available standard operating procedures and quality control assays will be needed. Prior to our new method there was no quality control assays available other than biological functional tests for extracellular vesicles. Also, the protein to lipid ratio is suitable to characterize different extracellular vesicle subpopulations to be used in the clinics. D. Development of anticancer drugs: The identification of new regulatory mechanisms in system overactive in tumor cells (for example EGFR and Src) could be useful to identify new therapeutic targets, and this could help in the development of new anti-cancer drugs. Outreach Activities: Our fellows were the Marie Curie Ambassadors and presented the work of the DYNANO to undergraduate and postgraduate students: Silviya STATEAVA (april 2014) at IIBM “Alberto Sols” Institute, UAM, CSIC, Madrid, Spain, Erol Licsandru (May 2013) at “Colegiul Matei Basarab” high school in Bucharest, Romania, Ioanna KALOGRAIAKI at the Universidad San Pablo CEU, Madrid, Spain, April 29, 2013 and at the School of Pharmacy, Aristotle University of Greece and Muhammet TANC at the UNIFI, Dept. NEUROFARBA, (April 2015) during a Seminar: European Commission Marie Skłodowska-Curie Actions. They created outreach videos see: Susanne SCHNEIDER (UDS) collaborated with the Valentina GARAVINI (CNRS –ICS) to produce a video which aimed at promoting the official DYNANO www.dynano.eu website and addressing the general public. Marta ABELLAN FLOS produced and edited a short video introducing her work at the CBO Lab in Namur. Press release: Brian TIMMER wrote an article for ‘Kemibladet’ in Swedish concerning his experiences in the DYNANO. Our seniors Mihai Barboiu was invited to give a presentation on the DYNANO during an H2020 Information Day on November, 19th 2014 in Montpellier. He highlighted that the aim of the project is to create the best conditions for exchange and interactions between disciplines, and between the fellows, their supervisors and external invited scientists. A multidisciplinary approach and team spirit are at the heart of such ITN projects. Moreover the coordinator Mihai Barboiu coordinated and give a lecture to Joffre High School - Montpellier on the occasion of Regional Chemistry Olympiads (Oct 2012). Press releases: The regional edition of the national Newspaper “Le Nouvel Observateur", France October 2014 (9 - 15) dedicates paragraphs on the ITN DYNANO. The article displays the logo and the address of the DYNANO website.
