Final Report Summary - INNOVCRETE (Unlocking the innovative capacity of multidisciplinary structural biology-driven research in Crete)
Executive Summary:
Structural biology techniques are presently developing at an increasingly rapid pace. Whereas these disciplines have traditionally been tackled as single entities, this approach is no longer sufficient to gain a detailed and quantitative understanding of the dynamic structure and biological context of the cell. Structural biologists have now recognized the need and advantage of combining and integrating several different techniques to resolve a single biological problem in all its complexities. These advances and the incredibly fast rate of development constitute new challenges and opportunities with enormous innovation potential and defined the concept of the InnovCrete project.
The strategic interest in an integrated approach to structural biology-driven research and the promises it holds have been clearly recognized also in Crete. For this reason, the scientists of the Institute of Molecular Biology and Biotechnology (part of the Foundation for Research and Technology – FORTH) in Heraklion (Crete) have merged in the InnovCrete project their experience, knowledge, energy and enthusiasm, not only to strengthen their competence and innovative capacities, but also to sustain and enhance their perspectives in the European Research Area and to actively contribute to the strengthening of structural biology initiatives in Europe. InnovCrete aims to create an environment for high-profile structural biology research in Crete, to sustain scientific and technological excellence, and to significantly enhance the innovative capacity of biomedicine/biology, biotechnology and biomaterials research in Crete. Managed by IMBB and including top-tier European research establishments and facilities as partners, InnovCrete is a multi-disciplinary research platform for established and emerging techniques in structural biology, biochemistry, biomedicine and molecular biology. It supports key areas techniques opening up the study of important biological macromolecules in Crete, including important drug targets.
Access to state-of-the-art structural biology in Crete for both academia and SMEs has been only one facet of InnovCrete. Its workshops, conferences and exchanges, in partnership with world-leading academic organizations and SMEs, have promoted and developed innovative, integrated approaches to structural biology and established interdisciplinary network activities across Europe. InnovCrete has promoted excellence in skills development, and encouraged cross-border performance of research projects. It enhanced significantly the innovation capacity of FORTH and the Region of Crete as a whole, through efficient IPR management mechanisms, training in IPR and innovation management and the creation of a portfolio of exploitable results and infrastructures.
InnovCrete has attracted experienced and early-stage researchers and has helped retain some of the most innovative and creative structural and molecular biology professionals in the Region of Crete. It has achieved scientific breakthroughs that will spread the benefits of innovation in the Region of Crete and across the European Union through strong links to scientific communities that share a passion for pushing the boundaries of existing scientific disciplines.
InnovCrete seeks also in future to increase the participation of its researchers to the EU RTD programmes. Its research is not be completely fundamental, but also contributes to solution of problems that are important for Crete, Greece and Europe as a whole in the areas of (a) Health-Biomedicine, (b) Agriculture/Food Security, (c) Biotechnology & Bio-inspired materials. Potentially exploitable results obtained in these fields are part of the technology portfolio of InnovCrete.
Project Context and Objectives:
Structural biology is a branch of molecular biology concerned with the molecular structure of biological macromolecules such as proteins, DNA/RNA and viruses. Resolving a molecule’s structure can give insights into the function of a molecule and eventually lead to drug targets, the development of new medicines, new bio-inspired nanomaterials etc. Structural biology and in particular the productivity of X-ray crystallography annd Free-Electron Lasers (FELs) is developing at an increasingly rapid pace. To determine the structure, proteins are usually crystallized, illuminated by X-rays, and the resulting diffraction pattern analyzed. This method of macromolecular crystallography is mainly carried out using X-rays generated at synchrotron facilities or conventional X-ray crystallographic facilities at structural biology laboratories. Furthermore the recent exciting demonstration of X-ray Free Electron Laser (XFEL) nano-crystallography has opened the door to a new era of structural biology. Apart from X-ray crystallography, structural biologists use many different techniques including Small Angle X-ray Scattering (SAXS), electron microscopy (EM), and a range of other biological/biomolecular imaging techniques. Whereas these disciplines have traditionally been tackled as single entities, this approach is no longer sufficient to gain a detailed and quantitative understanding of the dynamic structure and biological context of the cell. As each technique resolves structures at different resolutions and conditions, over the past few years, structural biologists have recognized the need and advantage of combining and integrating several different techniques to resolve a single biological problem in all its complexities. These advances and the incredibly fast rate of development provide new challenges and opportunities with enormous innovation potential. Synergies through the integration of structural biology with complementary research fields topic are turning into major innovation engines capable of meeting European development concerns and capable of sustaining economic growth and employment in Europe.
The strategic interest of structural biology-driven research and the promises it holds have been recognized as a clear thematic priority for development in Crete and created the basis for the InnovCrete project. For this reason, the scientists of the Institute of Molecular Biology and Biotechnology (IMBB) in Heraklion (Crete) and the wider academic community of Crete have merged in the project their experience and knowledge, so as to sustain and enhance their perspectives in the ERA and to actively contribute to the strengthening of innovative structural biology based initiatives in Europe. The coordinating institute IMBB was founded in 1983 and is part of the Foundation of Research and Technology-Hellas (FORTH), one of the largest research centers in Greece. IMBB hosts approximately 30 research groups and 160 scientists. Over the years IMBB has been ranked as the top Greek research centre in Biology, across all fields of research, by international panels of experts appointed by the Hellenic Ministry of Development. IMBB now is recognized as one of the most productive and internationally esteemed research communities of southern Europe, thanks to its high impact research results. In this favourable environment, the InnovCrete project aims to become a dynamic hub of structural biology providing researchers in Crete access to an integrated infrastructure of cutting-edge technology and scientific expertise. We seek to provide strategic leadership for structural biology at a European level by promoting an integrated approach to technology and methodologies.
The aim of InnovCrete is to create an environment for high-profile structural biology research in Crete, to sustain scientific and technological excellence in Biomedical and Life Sciences and to significantly enhance the innovative capacity of biomedicine/biology, biotechnology and biomaterials research in Crete in areas that fall within major priorities of the Innovation Union. Managed by IMBB and including top tier partners in the EU, InnovCrete represents a multi-disciplinary, multiscale research platform for established and emerging techniques in structural biology.
InnovCrete comprises all IMBB Departments and supports six key areas: (1) macromolecular X-ray crystallography, (2) biological SAXS, (3) advanced biological imaging, (4) physicochemical techniques (MALLS, CD, EM etc) as well as (5) protein production/high-throughput crystallisation and (6) molecular modelling. One future goal of the InnovCrete project is to support very challenging structural biology projects at IMBB through the exploitation of XFELs.
Installation and access to state-of-the-art structural biology for both academia and SMEs is only one aspect of the InnovCrete project. The InnovCrete workshops, conferences and secondments, in partnership with world-leading academic organizations and local/European SMEs, focus on promoting and developing innovative, integrated approaches to structural biology. By establishing and expanding interdisciplinary network activities across Europe, InnovCrete has promoted excellence in skills development, and encouraged cross-border performance of research projects and involvement in European Research Infrastructures. It furthermore enhanced significantly the innovation capacity of IMBB in the area o structural biology-driven research (molecular diagnostics, drug design, protein engineering, bio-nanomaterials etc) through the setting up of efficient IPR management mechanisms, training in IPR and innovation management and the creation of a portfolio of exploitable results and infrastructures. Through its contribution to the creation of Structural Biology Clusters InnovCrete has contributed to a broader innovation capacity building in the Region of Crete and the country as a whole. By catalyzing high quality collaborative research and through the upgrading of experimental facilities at IMBB, InnovCrete is in position to attract experienced researchers to Crete and help retain the most innovative and creative structural biology professionals of the country in the research centres of Crete. Through this integrated approach we aim to achieve breakthroughs in structural biology that are not possible with the previous infrastructure and spread the benefits of innovation across the Region of Crete and across the European Union.
We also seek to increase the participation of its researchers to the EU RTD programmes. In this context a strategy has been developed through scientific exchanges and the organization of workshops, conferences and seminars, to increase the visibility of excellence of IMBB research in the diverse fields of structural biology and its applications and to ensure the sustainability of strategic partnerships with top international research establishments and local/European SMEs.
InnovCrete research is not completely fundamental, but also contributes towards solving problems that are important for the region of Crete, Greece and Europe as a whole; these problems are highly relevant to present and future EU RTD programmes, i.e. making European science more innovative and competitive with the rest of the world, contributing to an increase of the wealth of Europe, and helping to overcome major socio-economic problems. InnovCrete addresses major EU and local priorities by focusing on major challenges facing society e.g. food security, health, bio-inspired technologies etc. Based on the research excellence and creativity of the IMBB scientists, the following scientific areas have been identified as promising sources of innovative ideas that can be turned in the future into products and services that create growth and jobs: (a) Health-Ageing, (b) Food Security, (c) Biotechnology & Bio-inspired materials, (d) Development/exploitation of Innovative Methods and Technologies.
The ultimate long-term objective supported under the InnovCrete action (also after termination of EU funding) is to turn IMBB into a leading European Centre of Excellence in structural biology, firmly integrated within the ERA, with a pool of competent and highly competitive researchers who are responsive to socio-economic regional or European development needs and capable of catalyzing innovation and the establishment of novel spin-offs and SMEs in the Region of Crete and in Europe. The InnovCrete initiative meets therefore perfectly the key priorities of EU, national and regional development policies.
In summary, InnovCrete has established since 2012 a state-of-the-art coordinated and multi-scale infrastructure for the exploitation of key methods in the 21st century structural biology in Crete. InnovCrete can now provide instrumentation and expertise for applications in six areas of structural biology: (i) biological small angle X-ray scattering; (ii) macromolecular X-ray crystallography; (iii) biological/biomolecular imaging; (iv)physicochemical techniques; (v) protein production, physicochemical characterization and high-throughput crystallisation; and (vi) molecular modeling. InnovCrete also cooperates with several partnering organizations and transnational/national networks which complement the infrastructure of IMBB and provide an integrated technology platform with all relevant methods in structural biology that are available in large-scale infrastructures.
Project Results:
InnovCrete: an integrating multidisciplinary project
The main result of the InnovCrete project is the establishment in Crete of a considerable scientific expertise in structural biology in combination with a state-of-the-art infrastructure, for the benefit of IMBB/FORTH scientists, the broader scientific community in Crete and several research oriented companies. The project has provided instrumentation and expertise in several areas: (i) biological small angle X-ray scattering; (ii) macromolecular X-ray crystallography; (iii) biological/biomolecular imaging; (iv) physicochemical infrastructure; (v) protein production, physicochemical characterization and high-throughput crystallisation; and (vi) molecular modeling. InnovCrete has also cooperated with several partnering organizations and transnational/national networks such as BioStruct-X, ESUO and Be/Opt-Xfel which complemented the infrastructure of IMBB by providing integrated technology platforms for all relevant methods in structural biology that are available in large-scale infrastructures.
With its instrumentation, networking and expertise, InnovCrete promoted multidisciplinary/multi-scale research, combining different methods and hybrid approaches. The research projects developed within the InnovCrete framework generate a significant potential for innovation at IMBB and considerable exploitation opportunities. This was clearly demonstrated by three projects which produced exploitable results for patent filing.
The InnovCrete projects are frequently very challenging and can be only tackled with the upgraded capacity for structural studies developed through InnovCrete. The creation of an integrated environment for protein production, characterization, crystallization and data collection has created bridges that efficiently link biology and biotechnology research at IMBB projects with structural methods.
The S/T results of InnovCrete listed in the following are a selection among a large number of collaborative projects; however these provide at this stage the most promising opportunities for exploitation:
Re-engineering of the folding pathways of α-helical bundles, new self-assembly modes and bio-inspired materials.
In the framework of InnovCrete project we elucidated the folding pathways of Rop protein, a paradigm of the 4-α-helical motif (Amprazi et al., 2014, PNAS).
Subsequently we re-designed helical bundles as building blocks for novel biomaterials (fibres, hydrogels etc) and characterized their properties by biophysical (Size- Exclusion Chromatography, Circular Dichroism, FTIR) and structural methods (protein crystallography, SAXS, electron Microscopy). In addition, we explored the implications of the “decoration” of the resulting constructs (helical scaffolds, fibres, hydrogels) with selected enzymatic domains, initially endonucleases. We found that the chimeric enzymes not only retain the activity of the attached endonucleases, but if different domains are attached and the geometries of the scaffolds are taken into account, novel, highly specific endonuclease activities can be developed. These chimeric enzymes have a vast spectrum of potential applications, e.g. in genome modifications and gene therapy. Due to the structural plasticity of helical proteins, we were able to develop highly stable helical scaffolds that are suitable for the development of enzymes that remain active in extremely harsh environments.
Two scaffold-based protein engineering approaches are at the stage of patent filing for a) novel enzyme engineering methods and b) engineering of novel bio-inspired materials.
Discovery of unusual post translational modifications associated with bacterial pathogenicity mechanisms
Posttranslational hydroxylation of proline (Pro) side chains has a key role in collagen biosynthesis, plant cell wall architecture and regulates critical cellular signaling and degradation processes. Its full extent has yet to be established, as its occurrence is probably significantly broader than previously perceived. Its role in various diseases and new therapies is only recently becoming clear. On the other hand, Pro hydroxylation in bacteria is largely unexplored.
We discovered a so far unknown Pro hydroxylation activity which occurs in active sites of polysaccharide deacetylases (PDAs) from bacterial pathogens, targeting the protein backbone to produce 2-hydroxyproline (2-Hyp). Crystallographic studies complemented by mass-spectrometry and mutagenesis reveal details for the Pro→2-Hyp conversion which is possibly autocatalytic, modifies with high specificity a conserved Pro, and utilizes the same active site and one of the catalytic residues as the deacetylation reaction. The origin of the oxygen of the hydroxyl group of 2-Hyp is molecular oxygen. By providing additional hydrogen bonding capacity, Pro hydroxylation alters the active site creating a more favourable environment for transition state stabilization, and thus potentially enhancing deacetylase activity. Although our results classify this process among the few examples of active site "maturation", it is atypical by being an intrinsic, backbone modifying activity, rather than an enzyme-catalyzed, side-chain modifying one. Our results pave the way for more detailed studies to explore the extent of 2-Hyp occurrence in eukaryotic and prokaryotic proteins as well as its implications in protein folding, stability and catalysis. More sophisticated concepts for PDA catalysis could improve our understanding of how Pro Cα hydroxylation affects defensive mechanisms of bacterial pathogens. Finally this work promises the development of novel antibiotics that target the maturation of PDA active sites in pathogens such as B. anthracis, B. cereus etc.
Studies of the Type III secretion system of plant pathogens
Pseudomonas syringae pathovars infect over 40 important crops worldwide and were deemed the most important bacterial plant pathogens. Infection involves gaining access and adapting to the plant’s apoplast, proliferation, secretion of type three helper proteins (T3H) and injection (translocation) of type three effector proteins (T3E) into plant cells via the Type Three Secretion System (T3SS). Translocated effectors can abrogate the plant immune defense, likened to switching off the burglar alarm. The plant tissue environment triggers a genetic pathogenesis program in Ps, which critically involves the expression of T3SS core genes, T3H as well as T3E genes. Plant tissue factors triggering Ps pathogenesis are poorly defined. The RNA polymerase activators HrpR-HrpS and one of their targets, the extra-cytoplasmic sigma factor HrpL are key transcription factors controlling all T3SS, T3H and T3E genes. HrpR-HrpS are negatively regulated by HrpV, whose activity is suppressed by HrpG. HrpJ of Ps is a protein of regulatory function and a secretion/translocation substrate itself; it is known to control the secretion of T3H and translocators, as well as the translocation of T3E, playing an additional role inside the plant following its translocation, which is suppression of host immunity.
We found that HrpJ directly binds to HrpG-HrpV complex, acting possibly as a modulator of the transcriptional activity of HrpRS, coupling transcriptional control and T3SS-mediated secretion. We have identified the existence of HrpG-HrpV, HrpG-HrpJ, HrpG-HrpV-HrpJ complexes both from Pseudomonas syringae pv. phaseolicola (Pph) and Erwinia amylovora (Eamy), using co-expression and co-purification strategies. We employed multi-angle light scattering to determine the molecular weight and molar ratio of the HrpG-HrpV-HrpJ reconstituted complex from Eamy, which was found to be around 76 kD (1:1:1 complex). Structural studies involving small-angle X-ray scattering have shown that the HrpG-HrpV-HrpJ complex is a particle similar to the determined structures of the respective complexes coming from animal pathogenic bacteria (YopN-SycN-YscB in Yersinia). Full expression analysis with quantitative real time PCR conducted in wild type Pph as well as in hrpG, hrpV and hrpJ mutants showed that HrpGV and HrpJ exert opposite function during T3SS activation; while HrpG-HrpV seem to suppress T3SS expression, HrpJ activates it. Ongoing data analysis of a full secretome analysis coupled to mass spectrometry in wild type Pph and hrpG, hrpV and hrpJ mutants will reveal the differences in the repertoire of secreted substrates for each strain that will allow us to determine the role of the complex and its subunits to regulation of T3SS secretion.
A range of proteins and complexes from the type III secretion system such as HrpE, HrpG, HrpV, HrpJ, HrcQAc, HrcQBc from different bacteria was analysed structurally with the help of protein crystallography and SAXS.
This work promises the development of novel antimicrobial agents that target key elements of the Type III pathogenicity mechanism.
Technologies for molecular diagnostics
These activities focus on two main research areas: the study of biomolecules conformation and of conformational changes induced by ligand binding and the coupling of such conformation-sensing events to the study of DNA molecules for molecular diagnostic purposes. During the last three years we showed several examples where biomolecular conformation was elucidated in a fully quantitative manner using acoustic wave devices and our newly developed model. Specifically, we showed the ability to detect acoustically multiple DNA targets by using a single probe; we studied with the acoustic device and AFM the structure of an intrinsically disordered protein, and changes upon its structure upon potassium binding; we also proved the hydrodynamic nature of DNA acoustic sensing by providing experimental evidence to back up our theoretical predictions. The use of acoustic wave devices for the quantitative determination of protein molecular weight was also published, while work on the characterization of the structure of calmodulin using the combined QCM/ellipsometry instrument is under development and will soon be published. In addition, the application of the above concepts to molecular diagnostics was described in a patent application, submitted to the UK patent office.
Potential Impact:
Although IMBB has consistently demonstrated in the past its capacity for excellence in research and innovation, there is every expectation that its international competitiveness, and innovative capacities will be improved significantly through the InnovCrete project. The project has been in a relatively short time able to catalyze innovations in the areas of Health & Biomedicine, Biotechnology and Bio-inspired nanomaterials. These will contribute to regional, national and European economic growth and quality of life, making a contribution in lifting Greece from its present economic downturn. Although these innovations originated from research projects that were already in progress at IMBB, they could be only achieved through the involvement of the InnovCrete technology platform. On the other hand, the project has also developed through networking considerable and beneficial synergies to other ongoing national activities (see WP6); these initiatves have already received national funding and will significantly promote innovation in biomedicine, biology and biotechnology in Greece, thus becoming engines for regional & national economic development. Key elements are thus gathered to make InnovCrete a scientific and economic success: the project is sustainable beyond the lifetime of REGPOT funding, and its scientific strategy and concepts are very innovative.
Better integration of InnovCrete in the European Research Area as a whole
The collaboration of the InnovCrete teams with EU academic partners that are renowned internationally for their expertise on all aspects of the project and the involvement of research-intensive SMEs offer the ideal synergy to turn the InnovCrete consortium into a leading European Centre of Excellence for structural biology, firmly integrated within the ERA. The involvement of high-profile partners in the rigorous seminars, conferences, trainings and workshops programme of InnovCrete, along with professional dissemination activities, has led to a broad recognition of the InnovCrete project and IMBB in the EU and a stable integration in ERA, thus considerably contributing to the InnovCrete impacts.
One further InnovCrete impact is the establishment of long-term strategic partnerships with its partners. This is reflected in activities aiming at the joint preparation of applications for EU funding, joint training activities (WP2), establishment of networks and interdisciplinary communities (BIOSTRUCT-X, BE/OPT XFEL, ESUO) etc. There is a high probability that these interactions will lead to bilateral research projects through EU funded and other programmes (INSTRUCT-EL has already received funding), producing joint innovation and training activities beyond the lifetime of the InnovCrete project. All innovations directly or indirectly resulting from InnovCrete (e.g. in the fields of gene therapy, drugs development, new bio-inspired materials, understanding of diseases and ageing, food security etc) meet major socio-economic and scientific development needs of the Region of Crete, the country and Europe, are consistent with Innovation Union priorities and will have a significant long-term impact in the ERA.
The international exposure, inflow of knowledge, the new technologies and methodologies, the new and upgraded instrumentation, along with the recruitment of a dynamic group of experienced researchers and the implementation of a career development plan has created a scientific culture in Crete which will be beneficial for the professional development of the research staff. Key elements in the ERA integration of InnovCrete are also the workshops, practical courses and conference programme of the project (WP4), which created a European tradition of excellent scientific meetings organized in Crete. This in turn will bring recognition of InnovCrete and IMBB among ERA scientists as a premium partner for collaborations.
Upgrading the RTD capacity and capability
The InnovCrete project has considerably upgraded the RTD capacity of IMBB in key areas of structural biology. This upgrade has been achieved a) through the significant strengthening of the human potential by means of the recruitment of experienced researchers (WP1) and b) the acquisition / upgrade of scientific equipment which put InnovCrete at a level comparable to very high European standards (WP3). The international exposure of InnovCrete scientists through the workshops/conferences programme, the improved skills for the preparation of grant applications (through special training courses) and activities for IP management, technology transfer and commercialization (WP5, WP6) will in near future catalyze increased external funding, which will be very beneficial for the continuous upgrading of the RTD capacity and capability and the quality of research in Crete. These improvements will be also very helpful for strategic research planning of individual research groups; at the level of IMBB as a whole, they will result in more focused research projects and a better critical mass of researchers capable of tackling challenging structural biology-driven projects.
Improved research capacity for increased contribution to regional economic and social development
InnovCrete has a strong involvement in regional initiatives (Agro-Food Cluster), will stay part of the Smart Specialization Strategy for the Region of Crete, the program for the development of the Knowledge complex/Key Enabling Technologies in Crete, and will further promote the establishment of national Clusters in Structural Biology.
Improved skills for participation in EU programmes
In order to improve the skills and know-how in the field of H2020 participation, workshops/practical courses on funding opportunities (WP5) and on IP and innovation management (WP6) have been organized. These offered training in grant application writing, research project management, including dissemination, commercialization etc. Equipped with these new scientific and managerial skills, the scientists from the Region of Crete will be much more capable of taking part in international competitive funding and European research collaborations. In addition, participation in EU projects is enhanced through the strategic partnerships (WP2, WP6) and the rigorous exchange programme. The upgraded RTD capacities will enhance the recognition of InnovCrete among leading European research groups as an excellent partner for EU programme proposals with specialist know-how and modern instrumentation.
Improved innovation potential
Crete is a particularly fertile ground for innovation in structural biology-driven research, as it includes the highest density of researchers in Life Sciences, and the two top rated research and academic institutions of the country (IMBB/FORTH and UOC). The RTD reinforcement through InnovCrete will produce applications for the biomedical, biotechnology and the bio-inspired materials sectors. Examples of such progress are new gene therapy tools based on gene replacement without the need for integrative gene therapy vectors, new antibacterial drugs, novel bio-inpired materials such as hydrogels and fibres with dimensions in the nano- to micro-scale region etc.
3.2 Spreading excellence, exploiting results, disseminating knowledge
The InnovCrete members have a commitment to knowledge dissemination and have used their existing networks, within academia, industry, policy and public administration to spread the information about InnovCrete activities, research achievements and regional development initiatives (WP5). Beyond that, longstanding relations with their colleagues in academia and the industrial sector in the EU and worldwide have been used to disseminate knowledge and scientific results and to strengthen the image of IMBB as a centre of excellence in structural biology research. In addition to classical dissemination tools (publications, TV, radio, newspapers), state-of-the-art electronic means (the InnovCrete web site, social media, see WP5), and communication materials (brochures, flyers, posters, etc.) have presented the project at the largest possible public front (details in WP5).
The diffusion of information to the scientific community has been transmitted through the publication of scientific articles in peer-reviewed journals and presentations as well as posters at national and international scientific conferences. To achieve an even higher recognition, InnovCrete has hosted in Crete the series of international conferences and workshops (WP 4) which significantly increased the impact of the project.
In the context of “excellence spreading”, regional training workshops and courses for skills training (on research funding, IP and innovation management, WP 4 & WP6) have been open to scientists from UOC or other Cretan research institutions (in addition to InnovCrete members). InnovCrete has also spread excellence and increased the impact of the project by providing access to its new equipment to other research groups for their own research.
With regard to the innovation and results exploitation dimension of InnovCrete, specific measures have been used for identifying potential partners and sources of finance for commercialization:
• Creation of an IPR/Technology Transfer Helpdesk for PR management
• Creation of a portfolio of exploitable results
• Participation in the largest international promotional and partnering events
• Collaboration with companies
• Organization of company missions to IMBB.
• Participation in Technology Transfer Brokerage Events
List of Websites:
Public website address:
www.innovcrete.eu
www.innovcrete.gr
Contact details:
Prof. Michael KOKKINIDIS
University of Crete/Dept. of Biology & IMBB/FORTH
P.O.Box 2208, Vassilika Vouton,
GR-71409 Heraklion/Crete, Greece
Tel. & Fax ++30-2810-394351; mobile ++30-6944-362871
Structural biology techniques are presently developing at an increasingly rapid pace. Whereas these disciplines have traditionally been tackled as single entities, this approach is no longer sufficient to gain a detailed and quantitative understanding of the dynamic structure and biological context of the cell. Structural biologists have now recognized the need and advantage of combining and integrating several different techniques to resolve a single biological problem in all its complexities. These advances and the incredibly fast rate of development constitute new challenges and opportunities with enormous innovation potential and defined the concept of the InnovCrete project.
The strategic interest in an integrated approach to structural biology-driven research and the promises it holds have been clearly recognized also in Crete. For this reason, the scientists of the Institute of Molecular Biology and Biotechnology (part of the Foundation for Research and Technology – FORTH) in Heraklion (Crete) have merged in the InnovCrete project their experience, knowledge, energy and enthusiasm, not only to strengthen their competence and innovative capacities, but also to sustain and enhance their perspectives in the European Research Area and to actively contribute to the strengthening of structural biology initiatives in Europe. InnovCrete aims to create an environment for high-profile structural biology research in Crete, to sustain scientific and technological excellence, and to significantly enhance the innovative capacity of biomedicine/biology, biotechnology and biomaterials research in Crete. Managed by IMBB and including top-tier European research establishments and facilities as partners, InnovCrete is a multi-disciplinary research platform for established and emerging techniques in structural biology, biochemistry, biomedicine and molecular biology. It supports key areas techniques opening up the study of important biological macromolecules in Crete, including important drug targets.
Access to state-of-the-art structural biology in Crete for both academia and SMEs has been only one facet of InnovCrete. Its workshops, conferences and exchanges, in partnership with world-leading academic organizations and SMEs, have promoted and developed innovative, integrated approaches to structural biology and established interdisciplinary network activities across Europe. InnovCrete has promoted excellence in skills development, and encouraged cross-border performance of research projects. It enhanced significantly the innovation capacity of FORTH and the Region of Crete as a whole, through efficient IPR management mechanisms, training in IPR and innovation management and the creation of a portfolio of exploitable results and infrastructures.
InnovCrete has attracted experienced and early-stage researchers and has helped retain some of the most innovative and creative structural and molecular biology professionals in the Region of Crete. It has achieved scientific breakthroughs that will spread the benefits of innovation in the Region of Crete and across the European Union through strong links to scientific communities that share a passion for pushing the boundaries of existing scientific disciplines.
InnovCrete seeks also in future to increase the participation of its researchers to the EU RTD programmes. Its research is not be completely fundamental, but also contributes to solution of problems that are important for Crete, Greece and Europe as a whole in the areas of (a) Health-Biomedicine, (b) Agriculture/Food Security, (c) Biotechnology & Bio-inspired materials. Potentially exploitable results obtained in these fields are part of the technology portfolio of InnovCrete.
Project Context and Objectives:
Structural biology is a branch of molecular biology concerned with the molecular structure of biological macromolecules such as proteins, DNA/RNA and viruses. Resolving a molecule’s structure can give insights into the function of a molecule and eventually lead to drug targets, the development of new medicines, new bio-inspired nanomaterials etc. Structural biology and in particular the productivity of X-ray crystallography annd Free-Electron Lasers (FELs) is developing at an increasingly rapid pace. To determine the structure, proteins are usually crystallized, illuminated by X-rays, and the resulting diffraction pattern analyzed. This method of macromolecular crystallography is mainly carried out using X-rays generated at synchrotron facilities or conventional X-ray crystallographic facilities at structural biology laboratories. Furthermore the recent exciting demonstration of X-ray Free Electron Laser (XFEL) nano-crystallography has opened the door to a new era of structural biology. Apart from X-ray crystallography, structural biologists use many different techniques including Small Angle X-ray Scattering (SAXS), electron microscopy (EM), and a range of other biological/biomolecular imaging techniques. Whereas these disciplines have traditionally been tackled as single entities, this approach is no longer sufficient to gain a detailed and quantitative understanding of the dynamic structure and biological context of the cell. As each technique resolves structures at different resolutions and conditions, over the past few years, structural biologists have recognized the need and advantage of combining and integrating several different techniques to resolve a single biological problem in all its complexities. These advances and the incredibly fast rate of development provide new challenges and opportunities with enormous innovation potential. Synergies through the integration of structural biology with complementary research fields topic are turning into major innovation engines capable of meeting European development concerns and capable of sustaining economic growth and employment in Europe.
The strategic interest of structural biology-driven research and the promises it holds have been recognized as a clear thematic priority for development in Crete and created the basis for the InnovCrete project. For this reason, the scientists of the Institute of Molecular Biology and Biotechnology (IMBB) in Heraklion (Crete) and the wider academic community of Crete have merged in the project their experience and knowledge, so as to sustain and enhance their perspectives in the ERA and to actively contribute to the strengthening of innovative structural biology based initiatives in Europe. The coordinating institute IMBB was founded in 1983 and is part of the Foundation of Research and Technology-Hellas (FORTH), one of the largest research centers in Greece. IMBB hosts approximately 30 research groups and 160 scientists. Over the years IMBB has been ranked as the top Greek research centre in Biology, across all fields of research, by international panels of experts appointed by the Hellenic Ministry of Development. IMBB now is recognized as one of the most productive and internationally esteemed research communities of southern Europe, thanks to its high impact research results. In this favourable environment, the InnovCrete project aims to become a dynamic hub of structural biology providing researchers in Crete access to an integrated infrastructure of cutting-edge technology and scientific expertise. We seek to provide strategic leadership for structural biology at a European level by promoting an integrated approach to technology and methodologies.
The aim of InnovCrete is to create an environment for high-profile structural biology research in Crete, to sustain scientific and technological excellence in Biomedical and Life Sciences and to significantly enhance the innovative capacity of biomedicine/biology, biotechnology and biomaterials research in Crete in areas that fall within major priorities of the Innovation Union. Managed by IMBB and including top tier partners in the EU, InnovCrete represents a multi-disciplinary, multiscale research platform for established and emerging techniques in structural biology.
InnovCrete comprises all IMBB Departments and supports six key areas: (1) macromolecular X-ray crystallography, (2) biological SAXS, (3) advanced biological imaging, (4) physicochemical techniques (MALLS, CD, EM etc) as well as (5) protein production/high-throughput crystallisation and (6) molecular modelling. One future goal of the InnovCrete project is to support very challenging structural biology projects at IMBB through the exploitation of XFELs.
Installation and access to state-of-the-art structural biology for both academia and SMEs is only one aspect of the InnovCrete project. The InnovCrete workshops, conferences and secondments, in partnership with world-leading academic organizations and local/European SMEs, focus on promoting and developing innovative, integrated approaches to structural biology. By establishing and expanding interdisciplinary network activities across Europe, InnovCrete has promoted excellence in skills development, and encouraged cross-border performance of research projects and involvement in European Research Infrastructures. It furthermore enhanced significantly the innovation capacity of IMBB in the area o structural biology-driven research (molecular diagnostics, drug design, protein engineering, bio-nanomaterials etc) through the setting up of efficient IPR management mechanisms, training in IPR and innovation management and the creation of a portfolio of exploitable results and infrastructures. Through its contribution to the creation of Structural Biology Clusters InnovCrete has contributed to a broader innovation capacity building in the Region of Crete and the country as a whole. By catalyzing high quality collaborative research and through the upgrading of experimental facilities at IMBB, InnovCrete is in position to attract experienced researchers to Crete and help retain the most innovative and creative structural biology professionals of the country in the research centres of Crete. Through this integrated approach we aim to achieve breakthroughs in structural biology that are not possible with the previous infrastructure and spread the benefits of innovation across the Region of Crete and across the European Union.
We also seek to increase the participation of its researchers to the EU RTD programmes. In this context a strategy has been developed through scientific exchanges and the organization of workshops, conferences and seminars, to increase the visibility of excellence of IMBB research in the diverse fields of structural biology and its applications and to ensure the sustainability of strategic partnerships with top international research establishments and local/European SMEs.
InnovCrete research is not completely fundamental, but also contributes towards solving problems that are important for the region of Crete, Greece and Europe as a whole; these problems are highly relevant to present and future EU RTD programmes, i.e. making European science more innovative and competitive with the rest of the world, contributing to an increase of the wealth of Europe, and helping to overcome major socio-economic problems. InnovCrete addresses major EU and local priorities by focusing on major challenges facing society e.g. food security, health, bio-inspired technologies etc. Based on the research excellence and creativity of the IMBB scientists, the following scientific areas have been identified as promising sources of innovative ideas that can be turned in the future into products and services that create growth and jobs: (a) Health-Ageing, (b) Food Security, (c) Biotechnology & Bio-inspired materials, (d) Development/exploitation of Innovative Methods and Technologies.
The ultimate long-term objective supported under the InnovCrete action (also after termination of EU funding) is to turn IMBB into a leading European Centre of Excellence in structural biology, firmly integrated within the ERA, with a pool of competent and highly competitive researchers who are responsive to socio-economic regional or European development needs and capable of catalyzing innovation and the establishment of novel spin-offs and SMEs in the Region of Crete and in Europe. The InnovCrete initiative meets therefore perfectly the key priorities of EU, national and regional development policies.
In summary, InnovCrete has established since 2012 a state-of-the-art coordinated and multi-scale infrastructure for the exploitation of key methods in the 21st century structural biology in Crete. InnovCrete can now provide instrumentation and expertise for applications in six areas of structural biology: (i) biological small angle X-ray scattering; (ii) macromolecular X-ray crystallography; (iii) biological/biomolecular imaging; (iv)physicochemical techniques; (v) protein production, physicochemical characterization and high-throughput crystallisation; and (vi) molecular modeling. InnovCrete also cooperates with several partnering organizations and transnational/national networks which complement the infrastructure of IMBB and provide an integrated technology platform with all relevant methods in structural biology that are available in large-scale infrastructures.
Project Results:
InnovCrete: an integrating multidisciplinary project
The main result of the InnovCrete project is the establishment in Crete of a considerable scientific expertise in structural biology in combination with a state-of-the-art infrastructure, for the benefit of IMBB/FORTH scientists, the broader scientific community in Crete and several research oriented companies. The project has provided instrumentation and expertise in several areas: (i) biological small angle X-ray scattering; (ii) macromolecular X-ray crystallography; (iii) biological/biomolecular imaging; (iv) physicochemical infrastructure; (v) protein production, physicochemical characterization and high-throughput crystallisation; and (vi) molecular modeling. InnovCrete has also cooperated with several partnering organizations and transnational/national networks such as BioStruct-X, ESUO and Be/Opt-Xfel which complemented the infrastructure of IMBB by providing integrated technology platforms for all relevant methods in structural biology that are available in large-scale infrastructures.
With its instrumentation, networking and expertise, InnovCrete promoted multidisciplinary/multi-scale research, combining different methods and hybrid approaches. The research projects developed within the InnovCrete framework generate a significant potential for innovation at IMBB and considerable exploitation opportunities. This was clearly demonstrated by three projects which produced exploitable results for patent filing.
The InnovCrete projects are frequently very challenging and can be only tackled with the upgraded capacity for structural studies developed through InnovCrete. The creation of an integrated environment for protein production, characterization, crystallization and data collection has created bridges that efficiently link biology and biotechnology research at IMBB projects with structural methods.
The S/T results of InnovCrete listed in the following are a selection among a large number of collaborative projects; however these provide at this stage the most promising opportunities for exploitation:
Re-engineering of the folding pathways of α-helical bundles, new self-assembly modes and bio-inspired materials.
In the framework of InnovCrete project we elucidated the folding pathways of Rop protein, a paradigm of the 4-α-helical motif (Amprazi et al., 2014, PNAS).
Subsequently we re-designed helical bundles as building blocks for novel biomaterials (fibres, hydrogels etc) and characterized their properties by biophysical (Size- Exclusion Chromatography, Circular Dichroism, FTIR) and structural methods (protein crystallography, SAXS, electron Microscopy). In addition, we explored the implications of the “decoration” of the resulting constructs (helical scaffolds, fibres, hydrogels) with selected enzymatic domains, initially endonucleases. We found that the chimeric enzymes not only retain the activity of the attached endonucleases, but if different domains are attached and the geometries of the scaffolds are taken into account, novel, highly specific endonuclease activities can be developed. These chimeric enzymes have a vast spectrum of potential applications, e.g. in genome modifications and gene therapy. Due to the structural plasticity of helical proteins, we were able to develop highly stable helical scaffolds that are suitable for the development of enzymes that remain active in extremely harsh environments.
Two scaffold-based protein engineering approaches are at the stage of patent filing for a) novel enzyme engineering methods and b) engineering of novel bio-inspired materials.
Discovery of unusual post translational modifications associated with bacterial pathogenicity mechanisms
Posttranslational hydroxylation of proline (Pro) side chains has a key role in collagen biosynthesis, plant cell wall architecture and regulates critical cellular signaling and degradation processes. Its full extent has yet to be established, as its occurrence is probably significantly broader than previously perceived. Its role in various diseases and new therapies is only recently becoming clear. On the other hand, Pro hydroxylation in bacteria is largely unexplored.
We discovered a so far unknown Pro hydroxylation activity which occurs in active sites of polysaccharide deacetylases (PDAs) from bacterial pathogens, targeting the protein backbone to produce 2-hydroxyproline (2-Hyp). Crystallographic studies complemented by mass-spectrometry and mutagenesis reveal details for the Pro→2-Hyp conversion which is possibly autocatalytic, modifies with high specificity a conserved Pro, and utilizes the same active site and one of the catalytic residues as the deacetylation reaction. The origin of the oxygen of the hydroxyl group of 2-Hyp is molecular oxygen. By providing additional hydrogen bonding capacity, Pro hydroxylation alters the active site creating a more favourable environment for transition state stabilization, and thus potentially enhancing deacetylase activity. Although our results classify this process among the few examples of active site "maturation", it is atypical by being an intrinsic, backbone modifying activity, rather than an enzyme-catalyzed, side-chain modifying one. Our results pave the way for more detailed studies to explore the extent of 2-Hyp occurrence in eukaryotic and prokaryotic proteins as well as its implications in protein folding, stability and catalysis. More sophisticated concepts for PDA catalysis could improve our understanding of how Pro Cα hydroxylation affects defensive mechanisms of bacterial pathogens. Finally this work promises the development of novel antibiotics that target the maturation of PDA active sites in pathogens such as B. anthracis, B. cereus etc.
Studies of the Type III secretion system of plant pathogens
Pseudomonas syringae pathovars infect over 40 important crops worldwide and were deemed the most important bacterial plant pathogens. Infection involves gaining access and adapting to the plant’s apoplast, proliferation, secretion of type three helper proteins (T3H) and injection (translocation) of type three effector proteins (T3E) into plant cells via the Type Three Secretion System (T3SS). Translocated effectors can abrogate the plant immune defense, likened to switching off the burglar alarm. The plant tissue environment triggers a genetic pathogenesis program in Ps, which critically involves the expression of T3SS core genes, T3H as well as T3E genes. Plant tissue factors triggering Ps pathogenesis are poorly defined. The RNA polymerase activators HrpR-HrpS and one of their targets, the extra-cytoplasmic sigma factor HrpL are key transcription factors controlling all T3SS, T3H and T3E genes. HrpR-HrpS are negatively regulated by HrpV, whose activity is suppressed by HrpG. HrpJ of Ps is a protein of regulatory function and a secretion/translocation substrate itself; it is known to control the secretion of T3H and translocators, as well as the translocation of T3E, playing an additional role inside the plant following its translocation, which is suppression of host immunity.
We found that HrpJ directly binds to HrpG-HrpV complex, acting possibly as a modulator of the transcriptional activity of HrpRS, coupling transcriptional control and T3SS-mediated secretion. We have identified the existence of HrpG-HrpV, HrpG-HrpJ, HrpG-HrpV-HrpJ complexes both from Pseudomonas syringae pv. phaseolicola (Pph) and Erwinia amylovora (Eamy), using co-expression and co-purification strategies. We employed multi-angle light scattering to determine the molecular weight and molar ratio of the HrpG-HrpV-HrpJ reconstituted complex from Eamy, which was found to be around 76 kD (1:1:1 complex). Structural studies involving small-angle X-ray scattering have shown that the HrpG-HrpV-HrpJ complex is a particle similar to the determined structures of the respective complexes coming from animal pathogenic bacteria (YopN-SycN-YscB in Yersinia). Full expression analysis with quantitative real time PCR conducted in wild type Pph as well as in hrpG, hrpV and hrpJ mutants showed that HrpGV and HrpJ exert opposite function during T3SS activation; while HrpG-HrpV seem to suppress T3SS expression, HrpJ activates it. Ongoing data analysis of a full secretome analysis coupled to mass spectrometry in wild type Pph and hrpG, hrpV and hrpJ mutants will reveal the differences in the repertoire of secreted substrates for each strain that will allow us to determine the role of the complex and its subunits to regulation of T3SS secretion.
A range of proteins and complexes from the type III secretion system such as HrpE, HrpG, HrpV, HrpJ, HrcQAc, HrcQBc from different bacteria was analysed structurally with the help of protein crystallography and SAXS.
This work promises the development of novel antimicrobial agents that target key elements of the Type III pathogenicity mechanism.
Technologies for molecular diagnostics
These activities focus on two main research areas: the study of biomolecules conformation and of conformational changes induced by ligand binding and the coupling of such conformation-sensing events to the study of DNA molecules for molecular diagnostic purposes. During the last three years we showed several examples where biomolecular conformation was elucidated in a fully quantitative manner using acoustic wave devices and our newly developed model. Specifically, we showed the ability to detect acoustically multiple DNA targets by using a single probe; we studied with the acoustic device and AFM the structure of an intrinsically disordered protein, and changes upon its structure upon potassium binding; we also proved the hydrodynamic nature of DNA acoustic sensing by providing experimental evidence to back up our theoretical predictions. The use of acoustic wave devices for the quantitative determination of protein molecular weight was also published, while work on the characterization of the structure of calmodulin using the combined QCM/ellipsometry instrument is under development and will soon be published. In addition, the application of the above concepts to molecular diagnostics was described in a patent application, submitted to the UK patent office.
Potential Impact:
Although IMBB has consistently demonstrated in the past its capacity for excellence in research and innovation, there is every expectation that its international competitiveness, and innovative capacities will be improved significantly through the InnovCrete project. The project has been in a relatively short time able to catalyze innovations in the areas of Health & Biomedicine, Biotechnology and Bio-inspired nanomaterials. These will contribute to regional, national and European economic growth and quality of life, making a contribution in lifting Greece from its present economic downturn. Although these innovations originated from research projects that were already in progress at IMBB, they could be only achieved through the involvement of the InnovCrete technology platform. On the other hand, the project has also developed through networking considerable and beneficial synergies to other ongoing national activities (see WP6); these initiatves have already received national funding and will significantly promote innovation in biomedicine, biology and biotechnology in Greece, thus becoming engines for regional & national economic development. Key elements are thus gathered to make InnovCrete a scientific and economic success: the project is sustainable beyond the lifetime of REGPOT funding, and its scientific strategy and concepts are very innovative.
Better integration of InnovCrete in the European Research Area as a whole
The collaboration of the InnovCrete teams with EU academic partners that are renowned internationally for their expertise on all aspects of the project and the involvement of research-intensive SMEs offer the ideal synergy to turn the InnovCrete consortium into a leading European Centre of Excellence for structural biology, firmly integrated within the ERA. The involvement of high-profile partners in the rigorous seminars, conferences, trainings and workshops programme of InnovCrete, along with professional dissemination activities, has led to a broad recognition of the InnovCrete project and IMBB in the EU and a stable integration in ERA, thus considerably contributing to the InnovCrete impacts.
One further InnovCrete impact is the establishment of long-term strategic partnerships with its partners. This is reflected in activities aiming at the joint preparation of applications for EU funding, joint training activities (WP2), establishment of networks and interdisciplinary communities (BIOSTRUCT-X, BE/OPT XFEL, ESUO) etc. There is a high probability that these interactions will lead to bilateral research projects through EU funded and other programmes (INSTRUCT-EL has already received funding), producing joint innovation and training activities beyond the lifetime of the InnovCrete project. All innovations directly or indirectly resulting from InnovCrete (e.g. in the fields of gene therapy, drugs development, new bio-inspired materials, understanding of diseases and ageing, food security etc) meet major socio-economic and scientific development needs of the Region of Crete, the country and Europe, are consistent with Innovation Union priorities and will have a significant long-term impact in the ERA.
The international exposure, inflow of knowledge, the new technologies and methodologies, the new and upgraded instrumentation, along with the recruitment of a dynamic group of experienced researchers and the implementation of a career development plan has created a scientific culture in Crete which will be beneficial for the professional development of the research staff. Key elements in the ERA integration of InnovCrete are also the workshops, practical courses and conference programme of the project (WP4), which created a European tradition of excellent scientific meetings organized in Crete. This in turn will bring recognition of InnovCrete and IMBB among ERA scientists as a premium partner for collaborations.
Upgrading the RTD capacity and capability
The InnovCrete project has considerably upgraded the RTD capacity of IMBB in key areas of structural biology. This upgrade has been achieved a) through the significant strengthening of the human potential by means of the recruitment of experienced researchers (WP1) and b) the acquisition / upgrade of scientific equipment which put InnovCrete at a level comparable to very high European standards (WP3). The international exposure of InnovCrete scientists through the workshops/conferences programme, the improved skills for the preparation of grant applications (through special training courses) and activities for IP management, technology transfer and commercialization (WP5, WP6) will in near future catalyze increased external funding, which will be very beneficial for the continuous upgrading of the RTD capacity and capability and the quality of research in Crete. These improvements will be also very helpful for strategic research planning of individual research groups; at the level of IMBB as a whole, they will result in more focused research projects and a better critical mass of researchers capable of tackling challenging structural biology-driven projects.
Improved research capacity for increased contribution to regional economic and social development
InnovCrete has a strong involvement in regional initiatives (Agro-Food Cluster), will stay part of the Smart Specialization Strategy for the Region of Crete, the program for the development of the Knowledge complex/Key Enabling Technologies in Crete, and will further promote the establishment of national Clusters in Structural Biology.
Improved skills for participation in EU programmes
In order to improve the skills and know-how in the field of H2020 participation, workshops/practical courses on funding opportunities (WP5) and on IP and innovation management (WP6) have been organized. These offered training in grant application writing, research project management, including dissemination, commercialization etc. Equipped with these new scientific and managerial skills, the scientists from the Region of Crete will be much more capable of taking part in international competitive funding and European research collaborations. In addition, participation in EU projects is enhanced through the strategic partnerships (WP2, WP6) and the rigorous exchange programme. The upgraded RTD capacities will enhance the recognition of InnovCrete among leading European research groups as an excellent partner for EU programme proposals with specialist know-how and modern instrumentation.
Improved innovation potential
Crete is a particularly fertile ground for innovation in structural biology-driven research, as it includes the highest density of researchers in Life Sciences, and the two top rated research and academic institutions of the country (IMBB/FORTH and UOC). The RTD reinforcement through InnovCrete will produce applications for the biomedical, biotechnology and the bio-inspired materials sectors. Examples of such progress are new gene therapy tools based on gene replacement without the need for integrative gene therapy vectors, new antibacterial drugs, novel bio-inpired materials such as hydrogels and fibres with dimensions in the nano- to micro-scale region etc.
3.2 Spreading excellence, exploiting results, disseminating knowledge
The InnovCrete members have a commitment to knowledge dissemination and have used their existing networks, within academia, industry, policy and public administration to spread the information about InnovCrete activities, research achievements and regional development initiatives (WP5). Beyond that, longstanding relations with their colleagues in academia and the industrial sector in the EU and worldwide have been used to disseminate knowledge and scientific results and to strengthen the image of IMBB as a centre of excellence in structural biology research. In addition to classical dissemination tools (publications, TV, radio, newspapers), state-of-the-art electronic means (the InnovCrete web site, social media, see WP5), and communication materials (brochures, flyers, posters, etc.) have presented the project at the largest possible public front (details in WP5).
The diffusion of information to the scientific community has been transmitted through the publication of scientific articles in peer-reviewed journals and presentations as well as posters at national and international scientific conferences. To achieve an even higher recognition, InnovCrete has hosted in Crete the series of international conferences and workshops (WP 4) which significantly increased the impact of the project.
In the context of “excellence spreading”, regional training workshops and courses for skills training (on research funding, IP and innovation management, WP 4 & WP6) have been open to scientists from UOC or other Cretan research institutions (in addition to InnovCrete members). InnovCrete has also spread excellence and increased the impact of the project by providing access to its new equipment to other research groups for their own research.
With regard to the innovation and results exploitation dimension of InnovCrete, specific measures have been used for identifying potential partners and sources of finance for commercialization:
• Creation of an IPR/Technology Transfer Helpdesk for PR management
• Creation of a portfolio of exploitable results
• Participation in the largest international promotional and partnering events
• Collaboration with companies
• Organization of company missions to IMBB.
• Participation in Technology Transfer Brokerage Events
List of Websites:
Public website address:
www.innovcrete.eu
www.innovcrete.gr
Contact details:
Prof. Michael KOKKINIDIS
University of Crete/Dept. of Biology & IMBB/FORTH
P.O.Box 2208, Vassilika Vouton,
GR-71409 Heraklion/Crete, Greece
Tel. & Fax ++30-2810-394351; mobile ++30-6944-362871
