Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development

Final Report Summary - INNOMOL (Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development)

Executive Summary:
EU boosts research in Croatia - an EU initiative is strengthening the infrastructure of one of the leading research institutes in Croatia.
Overcoming major healthcare challenges such as cancer and autoimmunity is of primary importance for the European Union. To develop new diagnostic, preventive or therapeutic approaches for these diseases, Europe needs to invest in relevant research and technology transfer activities.
The EU-funded InnoMol (Enhancement of the innovation potential in SEE through new molecular solutions in research and development) initiative aimed to foster a research pipeline at the Ruđer Bošković Institute (RBI) in Croatia. The scope was to facilitate new avenues of innovation and technology for the investigation of relevant diseases. Through the establishment of a centre of excellence, InnoMol had aimed to close the gap between research and valorisation of innovative products. Among the objectives of the initiative was the unlocking and development of the research potential of the Institute so as to render RBI a dynamic leader in Molecular Bioscience research in South Eastern Europe. For this purpose, RBI recruited seven experts in the fields of Medicine, Biology, and Chemistry. New resources and equipment have been purchased to complement the existing scientific platforms of genomics, proteomics and imaging. A significant part of the project involved networking with EU partners to strengthen RBI research and participate in research activities at the community level. So far, RBI researchers and collaborators have submitted several Horizon 2020 project proposals. Further input from EU partners will contribute towards strengthening and implementing an IP management plan to help build a framework for innovation capacity. Dissemination activities included the organization of international conferences, media appearances, press releases, posters and presentations at numerous events. Taken together, the InnoMol efforts were designed to upgrade the research and technology capacity of RBI and become established in Molecular Biosciences research. They were also conceived to forge strategic partnerships between RBI and appropriate enterprises, thereby contributing towards the translation of research findings into marketable services and products. InnoMol proved that by joining forces, leading scientists were capable of managing a complex and multidisciplinary project. It created an atmosphere of departure, to leave the old strategy where everybody persisted in their own field, and move on to endeavouring to work in a new challenging, promising and overarching research field.
RBI now has the most advanced genomics platform, which will allow R&D for genetic testing, for example development for custom–tailored tests for any genetically assessable disease. Such technology use has huge potential in several respects. For example, job creation for certain profiles of scientists such as bioinformaticians, and data analysts, but also experts in product development, molecular biologists and biochemists. The RBI is also collaborating with SMEs to develop new clinical diagnostics approaches. Furthermore, the researchers are using a genomics platform to upgrade the services of the Croatian health insurance system for precise and personalized medicine.
Ultimately, InnoMol has opened up new avenues for R&D, as well as serving as an example for entrepreneurship in Croatia and the surrounding region, thanks to its creation of start-ups.

Project Context and Objectives:
The major aim of InnoMol is to improve the scientific and socio-economic impact of Life Sciences related Divisions at the Ruder Boskovic Institute, by the acquisition of high-level equipment for Genomic and Molecular Biological technology that was complemented by experienced human resources and international exchange of knowledge and technology. On longer term, diagnostic and therapeutic applications are envisioned.
InnoMol managed to gather three worlds within the life sciences – biology, chemistry, and biomedicine – in order to generate synergy in order to enable a research pipeline designed to allow research from single molecules to concrete solutions in the health and/or life sciences domains. The decision was made to utilize inter- and multidisciplinary approached in order to maximise the research environment that exists at the Ruđer Bošković Institute (RBI), Croatia.
The fully assembled research pipeline will enable inter- and, multidisciplinary research in the field of Molecular Biosciences with focus on DNA-Protein, Protein-Protein, Protein-RNA, DNA-RNA and DNA-DNA interactions. Such pipeline will enable elucidation of molecular processes in health and disease from different angles using a variety of molecular approaches, and thus increase innovation potential in order to contribute to new avenues of Molecular Biosciences research.
Beginning with molecular design, the pipeline involves the synthesis of novel organic compounds, which can then be tested for activity towards a large number of DNA, RNA and protein targets. Those compounds exhibiting promising medicinal properties can be used as leads in the rational development of new, and potentially more potent, molecules. On the other hand, substances that appear relatively inert can be refined into efficient markers for use in bio-imaging and testing. The effective implementation of a pipeline of this kind, which is the goal of the InnoMol team, will require optimization on numerous levels across several scientific disciplines.
Thus, InnoMol will establish a core of a think-tank to combine the best knowledge of the three worlds “Medicine”, “Biology” and “Chemistry” providing multiscale molecular solutions to derive predictive, quantitative and practical models for biological systems. Strong bioinformatics support will provide cohesion within the research pipeline, and thus maximise its output by unlocking data generated by high-throughput applications such as microarrays and mass spectrometry.
Present human resources will be strengthened by exchange of Know-How with high-profile partnering organisations. Scientific fields where InnoMol is less present will be enhanced by recruitment of experts to increase capacities and capabilities.
In that context, RBI is seeking opportunities to collaborate with SME industry in order to engage in new innovation to contribute to sustainability. InnoMol will aid in fostering such envisaged collaborations through the established research pipeline that will comprise the S&T backbone for enabling RBI to excel beyond the State-of-the-Art.
In particular, InnoMol will accelerate the pace of discoveries of human genetic variation by using latest NGS technology, and translate the basic science discoveries into new biomarkers to assess the contribution of genes and gene-environment interactions (behaviour, nutrition, chemicals, and other exposures) to individual and population risks for various cancers. Without the expansion of population sciences in genomics, the promise of genome research and discoveries may not reach its full potential.
New S&T capacities and capabilities of RBI will be introduced to public and professional audiences through workshop activities and conferences. This will highlight new opportunities for diagnostics and basic research in the SEE region, exposing RBI as driving force in the Molecular Biosciences.
Community support will improve presence of RBI researchers abroad through participation at high profile international conferences and meetings. Interaction with leading experts in Molecular Biosciences research may aid in exchange of ideas, and may initiate national and international collaboration that will contribute in broadening and tightening networks, and a better integration of RBI in the ERA.

Summary objectives:

• Shed light on the dynamic processes within living organisms to better understand the causes and potential treatment of genetic diseases.
• Lessen the healthcare burden through the enhancement of research into the diagnostic, preventative and therapeutic approaches to major diseases such as cancer, autoimmune diseases and degenerative diseases amongst others.
• Open up new avenues for R&D in Croatia.

Project Results:
The work performed is bundled in the InnoMol Action plan that includes a coherent set of 4 measures:

• Measure 1: Recruitment;
• Measure 2: Twinning;
• Measure 3: Research Equipment;
• Measure 4: IP development;

organized into seven Work Packages. The Work Packages were conceived to either directly address the above measures or to provide coordination and support towards their realization.
Addressing these measures, S&T results have been obtained as follows:
1.1.3.1 Work Package 1: Recruitment
The objectives of WP1 were to (1) Enhance knowledge and know-how of RBI by hiring experienced researchers, and (2) Strengthen human resources in areas that are inadequately covered by present RBI staff. These objectives were undoubtedly met during the project, thus creating a productive, state-of-the-art environment, with exploitable results described in Section B.
The initially envisaged expert positions, e.g. 7 planned positions with an optional 8th position (see ANNEX I, Description of Work) resulted in employment of altogether 10 individuals who filled the aforementioned maximimum 8 available positions successively. Because some experts left the project before its end due to other job opportunities, we filled vacancies accordingly. Positions were filled by foreigners, nationals, or returning nationals, thereby contributing to some extent to reverse 'brain drain' effects.
In particular, it is worthwhile to point out is that during reporting period 2, the hired IP manager allowed effortless preparation of two patent applications originating from InnoMol support (Table B1, confidential data).
1.1.3.2 Work Package 2: Exchange & Secondments
The main objectives of WP2 are to (1) Strengthen the existing research potential of RBI and (2) Help to strengthen the S&T capacities of RBI researchers to successfully participate in research activities at Community level and the FP7 programme, and beyond (Horizon 2020). The goal was to improve the human resources of RBI to keep up with international standards, and to strengthen the overall research potential.
To achieve these objectives, and to realize the requisite exchange of know-how, a series of trans-national two-way secondments of research staff of the RBI and 36 knowledgeable and experienced 'partnering organisations' in 10 EU Member States and 1 associated State have been organized.
In total, scientists from the Ruđer Bošković Institute spent 76,7 out of 101,5 envisaged person/months at secondments visiting 33 of 36 partner institutions and 51 out of 54 tasks were successfully completed during the project, which amounts to 75% of total planned outgoing secondments in terms of time spent at the foreign institutions. Several institutions, such as ALMF, HUGI, IBMB, ILAN and BIO, were particularly frequently visited, even more than initially planned, whereas some others (PRO, UNIMAN, VUB, CBM and UNIROMA) were visited to a lesser extent than initially planned.
Undoubtfully, human resources have been upgraded through altogether 46 exchange secondments involving 33 of the 36 partnering organisations spread throughout the ERA.
Secondees established contacts with leading experts in the field (at partnering organizations). The intensive networking resulted in several new international projects including InnoMol partners, thereby contributing to sustainability of research of InnoMol staff, using established State-of-the-Art equipment. Gathering experience in leading projects will be important for further advancing careers and driving cutting-edge science. Joint experiments have been performed, new methods have been acquired, and scientific services that are not yet available at RBI have been consumed at partner institutions. Last but not least, networking with InnoMol partners resulted in numerous national and international proposals where partnering organizations are participating as collaborators or consultants. Also, submission of Horizon 2020 project proposals, although not funded fostered the ‘good practices’ for continuing collaborations on all levels. One proposal is still under evaluation, H2020-WIDESPREAD-04-2017-Teaming Phase1 (Proposal BioMedMode, project ID 763595), which might serve as an opportunity for creating a Centre of Excellence for molecular biosciences at RBI.
1.1.3.3 Work Package 3: Equipment Implementation & Exploitation
The objectives for WP3 were to: (1) Engage in innovation and cutting edge technology, (2) Enable partnership with SME industry, (3) Serve as gateway for accessing resources, skills, and technology new to the regional community, (4) Strengthen IRB Core Facilities, and (5) Stimulate the realisation of sustainability after project closure.
The main tasks of WP3 are the purchase or upgrade of capital equipment, followed by testing and eventual troubleshooting if needed. The majority of the instruments were acquired according to the schedule. The staff employed via InnoMol attended producer organized seminars to get hands on experience, as foreseen. Similarly, all foreseen visits to collaborating groups directly related to instrumentation were realized, adding to the experience of each group responsible for major instrumentation.
The resources available at RBI have been complemented by the EC contribution and feature the major scientific platforms of genomics, proteomics and imaging, linked together through the envisaged pipeline. During the life of the project major equipment for the Bioimaging, Molecular interactions, and the Genomics platforms has been acquired. In particular the Next Generation Sequencing (NGS) unit has been able to be exploited scientifically and commercially. The NGS platform features the latest development lines of that kind of equipment, released in 2015 and 2016, respectively, representing breakthrough sequencing technology for small sample sets, not available before 2016.
Furthermore, it is now possible to use the genomics platform to upgrade the services of the Croatian health insurance system for precise and personalized medicine. Offering advanced genetic testing, for example in cancer prevention, most common to the wider public is breast and ovarian cancer genetic testing, we are closing in on world wide standards for application of new cancer therapies that rely on genetic testing prior therapy. Additionally, through unprecedented insights into the genetics of human disease, InnoMol has the potential to boost the public health sector of SEE and contribute by dramatically decreasing overall costs for genetic analysis, and increasing capabilities to tackle yet unknown diseases in order to provide better or new therapies.
Careful consideration has been given to the scientific evolutions during recent years in technology or structural and cellular biological applications. Imaging technology has made huge progress for cellular imaging of life cells in physiological conditions and changes in the environment programmed from hormone like human or other mammalian proteins or hormones that can be followed in time-lapse experiments. Therefore, the new confocal microscope is an essential tool for upgraded cellular biology which can be applied for the development of new therapeutics.
This technology also touches new developments in the Division of Organic Chemistry where new fluorescent dyes are being developed. Quantification of specific interactions within or at the surface of the cell are made possible by better image analysis software. For higher level application of image analyses software, the ICT Division could play an important supportive role. Three-dimensional imaging requires much more advanced software where there is room for improvement and animations would be very useful instruments for dissemination to the general public or for educational purposes in high schools and universities.
To date, the project has seen success in generating and sustaining new jobs, with InnoMol recruited staff having received permanent job positions at several institutions, including private companies, universities, and at RBI. InnoMol has also commercialised equipment, with nearly all of the acquired equipment being open access. Private companies, the academic sector, and RBI internal staff have access and pay for usage. Generated future revenue will be reinvested in employment of additional experts.
RBI now has the most advanced genomics platform, which will allow R&D for genetic testing, for example development for custom–tailored tests for any genetically assessable disease. Such a next-generation-sequencing market has huge potential in several respects. For example, job creation for certain profiles of scientists such as bioinformaticians, and data analysts, but also experts in product development, molecular biologists and biochemists, thereby successfully contributing to smart specialization in the STEM field. The RBI is also collaborating with SMEs to develop new clinical diagnostics approaches.
Finally, InnoMol is opening up new avenues for R&D, as well as serving as an example for entrepreneurship in Croatia and the surrounding region, thanks to its creation of start-ups.

1.1.3.4 Work Package 4: IPR Management
The objectives for WP4 were to (1) Develop the plan for IP management, and (2) Integrate InnoMol scientific output to the knowledge database of RBI.
WP4 contributed in recognizing emerging IP form RBI research activities, which resulted in two patent applications (confidential, Table B1).
WP4 engaged in preparation of new RBI’s Rules of intellectual property and conflict of interest, and in IPR counselling and advising especially regarding existing RBI’s patent portfolio. Additionally, training missions allowed deep insights and fostered practical knowledge for supporting IP and knowledge transfer identification, principles & procedures, and commercialization, enhancing overall knowledge at RBI in regard to certain aspects of IP management.
1.1.3.5 Work Package 5: Dissemination & Visibility Activities
The objectives of WP5 were to: (1) Increase visibility of RBI and stimulate its promotion as centre of excellence in Molecular Biosciences in South Eastern Europe, (2) Disseminate InnoMol objectives and results addressing specific stakeholder's priorities, (3) Demonstrate capabilities of new research pipeline to offer new molecular solutions in research and development, and (4) Stimulate networking and realisation of synergies with other European initiatives related to InnoMol.
1.1.3.6 Work Package 6: Management
The primary objective of the Management Work Package was to ensure the smooth running of the project. An important role in this respect is the coordination between the project scientists, on one hand, and the RBI’s administrative services, on the other. Namely, in order to respect the local practices, regulations, and legal framework in project implementation, frequent intervention and problem-solving is required by the WP6 team. Particular attention was paid to procurement and employment procedures as well as ensuring all appropriate documentary evidence (in collaboration with the Office for Projects) was generated and stored in an adequate manner.
1.1.3.7 Work Package 7: Ex-Post Evaluation
The objectives of WP7 were to (1) provide an efficient interface between InnoMol, independent experts and regional authorities and (2) to stimulate the uptake of recommendations of independent evaluators for preserving emerging excellence for the Molecular Biosciences. Apart from attendence of the Game of Epigenomics conference in Dubrovnik in April 2016, the evaluators made trips to the RBI in Zagreb from June 19-22 and October 25-27 in 2016.
1.1.3.8 Summary for InnoMol project
The overall summary of person/months reosurces commited to the InnoMol project are shown below:
Work Package 1 340.4
Work Package 2 44.7
Work Package 3 40.3
Work Package 4 24.6
Work Package 5 68.1
Work Package 6 74.2
Work Package 7 6.0
The summary of person/month involvement for InnoMol was 598.3 out of foreseen 593 person/months
Financial summary for the InnoMol project states that a total cost of 4,432,561.43 EUR occurred.

Potential Impact:
Significant impacts are expected in the three worlds “Medicine”, “Biology” and “Chemistry”.
1. InnoMol featured partnering with 33 out of 36 envisaged European high-profile organizations. Undoubtedfully, InnoMol networking should lead to a better integration of the Ruđer Bošković Institute (RBI) in the ERA. On one hand, partners have already a well established network of collaborators. RBI on the other hand will continue to broaden and tighten networking with groups elsewhere in Europe through the existing network of partners, and beyond. To do so, RBI offers several model system for Epigenetics and methylome research, such as common cancers (breast, lung, colon), a new human disease discovered recently, and not available elsewhere in the world (AHCY deficiency), and Neurodegenerative Diseases (Alzheimer, PTSD). Thus, InnoMol will expand RBI activities to new techniques and skills within the Epigenomics field to make it more competitive in contracting with national and international organizations. Importantly, secondees will be able to capitalize upon contacts with leading experts in the field (at partnering organizations). Being integrated in ERA will be important for developing their careers as future group leaders. Further, partners MPI, IRI, HUGI and CEINGE are dynamic actors in the methylation field and highly enthusiastic to collaborate on basis of available model systems. Upgrading of RTD capacities and capabilities through community support should expose RBI as attractive partner in the ERA for future partnerships. Networking with partner institutions working on state-of-the art platforms for eScience and bioinformatics will initiate new scientific collaborations and increase chances to participate in Horizon 2020 projects. Know-how on construction of semantically enabled knowledge bases and automated workflows for data analytics should provide an effective means for merging and intelligent utilization of data flowing from the InnoMol experimental platform, with a multitude of publicly available data and knowledge sources.
2. InnoMol will upgrade the RTD capacity and capability at RBI through improving human resources by future exchange of Know-How and knowledge with partnering organizations of high profile. Positive side effects are fostering European thinking. Recruitment of experts within the S&T domain of RBI will lead to enhancement of scientific expertise that is inadequately covered by present RBI staff, and will reverse 'brain drain' effects in South Eastern Europe. Thus, bringing together a critical mass of experts in molecular biosciences research, bioimaging, array technology and bioinformatics to complement and upgrade RTD capacity and capability is important for the global goal of RBI to become a leader in the Molecular Biosciences in SEE region. Quality of research carried out by RBI researcher will be enhanced through the assembled InnoMol research pipeline that is unique in Croatia, and probably is one of its kind in South Eastern Europe. The new platform represents a major leap for RBI capabilities towards Molecular Biosciences research, as it covers Genomics, Proteomics, Bioimaging and Bioinformatics, and High-Throughput technologies from third generation sequencing to array technology, mass spectrometry, spectroscopic techniques, advanced microscopy, biomolecule modeling, and active compound design. The technological platform gives Scientists, Clinical Physicians and Research managers access to basic research and clinical application, and diagnosis, whereas RBI will provide S&T support and expertise to suit needs of the scientific community in order to transfer technology and Know-How. Importantly, the RTD platform is based on an 'open source' concept enabling services and use for commercial activities, to all major Croatian research laboratories and industries, and the wider region (SEE). Efficient crosslinking of Genomics and Proteomics will excel RBI RTD capacity beyond the State-of-the-Art. The envisaged outcome is that RBI will become a leader in South Eastern Europe in Molecular Biosciences.
3. InnoMol will lead to improved research capacity at RBI for increased contribution to regional economic and social development. Increasingly, academic institutes and biotechs are forging alliances with the industry to develop and commercialise their products. There are significant market opportunities for new epigenetic therapies and biomarkers in a variety of disease areas although the most advanced area is oncology. The success of the first generation broad spectrum products should ensure future investment in this complex and multidisciplinary scientific field. Impacts are expected through partnership between RBI and clinical institutions due to experience in rare inherited diseases such as AHCY deficiency that was discovered in 2004 with RBI involvement and expertise in molecular diagnostics. By joining forces, new diagnostic approaches for similar disease may be developed that are based on State-of-the-Art approaches, for example Next-Generation-Sequencing (NGS). Custom prototype genetic panels of any kind for genetic disease analysis can be validated on the advanced genetics platform established through InnoMol.
4. InnoMol will improve significantly the potential of RBI to participate in Horizon 2020 projects. Concretely, featuring a innovative research pipeline will raise interest among the ERA to collaborate with RBI, and to include RBI as dynamic partner in projects lead by high-profile entities within Europe. Enhanced human resources including recruited experts operating the new platform will foster RBI engagement in the field of protein-protein and protein-DNA interactions, which is a particular topic in several Horizon 2020 calls. Thus, participation in Horizon 2020 projects at higher frequency is expected. At present moment, InnoMol is in line with the Horizon 2020 HEALTH programme and other themes such as European Technology Platforms (ETPs), the European Light Microscopy Initiative (ELMI) and, in particular, the European Strategic Forum on Research Infrastructure (ESFRI). Importantly, with the new platform, RBI might become an attractive partner for Horizon 2020 Calls targeting SMEs (Research to the benefit of SMEs, outsourcing initiatives etc.). Additionally, increased potential to apply to Horizon 2020 programme and its successors will contribute to sustainability of the project beyond project closure.
Finally, RBI will act a role model for success in FP7, and provide motivation for other groups in Croatia to follow its steps to raise overall RTD capacities elsewhere in the region, and at RBI.

List of Websites:
www.innomol.eu

Coordinator: Oliver Vugrek; ovugrek@irb.hr; skype: oliver.vugrek

Final Report Summary - INNOMOL (Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development)

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