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Strengthening Regional Bioresearch Potential in Greece: Advanced scientific performance at the Department of Molecular Biology and Genetics in Thrace

Final Report Summary - BIOSTRENGTH (Strengthening Regional Bioresearch Potential in Greece: Advanced scientific performance at the Department of Molecular Biology and Genetics in Thrace)

Executive Summary:
The Department of Molecular Biology and Genetics (MBG) is situated in Thrace, at the crossroad between Europe and Asia. It is the only faculty in Greece providing a curriculum on molecular biology and genetics. MBG excels in basic research, answering key biological questions with application in understanding the molecular basis of human diseases. Project BioStrength has been a major contributor of building the infrastructure and R&D capacity of the department, increasing visibility and fostering collaborations towards realization of MBG’s vision of becoming a centre of research excellence in South East Europe.
Specifically, under BioStrength we setup and operate the Cell Imaging and Biomolecular Interactions (CiBIT) core facility, a high-end unit which focuses in the areas of Bioimaging and Biomolecular interaction analysis. CiBIT is equipped with unique in Greece state-of-the-art equipment, a customized multi-laser line modular confocal microscope and a multiplex surface plasmon resonance (SPR) biosensor. The unit operates as internal and external (from mid 2011) service providing advanced cellular imaging and characterization of in vitro macromolecular and target-drug interactions with support from dedicated scientific staff of international expertise. It is expected that CiBIT will sustain its function as a research and training pole, of great interest to the Greek scientific community and the wider Balkan research area.
The project has also enhanced dynamic research and training links with knowledgeable institutions and partners via short-term visits (outbound and inbound). Transfer of knowledge and CiBIT’s training capacity has been further enhanced via successful organization of a hands-on workshop under the project. Our main partners included the Advanced Light Microscopy Facility of EMBL-Heidelberg, the Technology Facility of University of York, Friedrich Miescher Institute of Novartis Research Foundation-Basel and Center of Genetic Research, Barcelona. In addition, a number of other European research centers have been used in our knowledge-transfer network.


Project Context and Objectives:
The Department of Molecular Biology & Genetics (MBG) of Democritus University Thrace set out to take advantage of the specific topics addressed by Activity 4.1 “Unlocking and developing the research potential in the EU’s convergence regions and outermost regions” of the FP7-Research Capacities programme-REGPOT-2008-1, towards the convergence with the R&D ranking of EU education and research units of similar size. Project BioStrength was funded under REGPOT with 1 million Euros. The project contributed significantly towards further advancement of the research potential of MBG and the realization of the following objectives:

1. To perform high-quality research in key areas of the molecular biosciences with impact not only to the National research charter and the regional socio-economic development but also to Europe and internationally.
2. To fully integrate in the European Research Area (ERA) and become a centre of scientific excellence in SE-Europe and a Balkan area at the cross road between EU, Asia and Russia.
3. To further support and enhance existing collaborative efforts with other research units within the EU and to engage in sustainable knowledge-exchange programs with partners or twin organizations.
4. To achieve synergies with technology/research-oriented SMEs and the industrial sector to promote regional commercialisations of R&D results and support the economic development of Thrace.
5. To develop innovative technologies and know-how for the benefit of human lives in line with EU directive to combat major diseases like cancer, malaria, TB and other.
6. To provide high impact training and technology transfer programmes to researchers and stakeholders for the advancement of individual careers and the establishment of partnerships with SMEs and industrial organizations.
7. To support strong visibility actions and foster the spread of knowledge to maintain a strong reputation among the scientific community and the society overall, contributing to the improvement of the social fabric by increasing public awareness for the biosciences as well as advancing the regional and National economic level.

The anticipated benefits of BioStrength project included:

1. Reinforcement of the S&T potential of the Department by an increased involvement in high-impact research and technological development.
2. Increased mobilization of highly skilled human resources in a typical rural area.
3. Development of a strong technology basis towards the development of concrete research units/facilities.
4. Development of strategic partnerships and twining with advanced European research centres for training and knowledge-exchange.
5. Promotion of technology-transfer actions to and from researchers, SMEs and industries through specific workshops.
6. Increased competitiveness in attracting EU funding and participation in EU-funded research networks or programmes.
7. Increased visibility and reputation of MBG and the enhanced awareness of the research community and the public for research and training actions of MBG through dissemination, promotion and conference activities.

Through BioStrength the Department of Molecular Biology and Genetics excelled its ongoing research capability and strategic placement in Greece and improved its level of establishment as a leading center of excellence at SE-Europe and the Balkans, a region crucial for the enlarged European Union.
Successful implementation and sustainability of the project was based on measurable indicators for project’s objectives via implementation of project Work Packages (WPs). These indicators included:

• Long-lasting research collaborations
• Research partnership agreements
• Increased research publication rate
• Increased interaction with peer researchers via workshops and conference
• Joint scientific publications
• Joint scientific publications or joint patent applications
• Increased research publication rate
• Number of research and exchange of information seminars from researchers and partnering organizations
• Number of visits at public domain website

BioStrength proposed and successfully implemented a comprehensive action plan which was composed of five parts:

1. A two-way exchange of knowledge and visiting programme between MBG faculty members and selected European research and training centres of excellence and in-bound visits from individual researchers. Our main partners included the Advanced Light Microscopy Facility of EMBL-Heidelberg, the Technology Facility of University of York, Friedrich Miescher Institute of Novartis Research Foundation-Basel and the Center of Genetic Research, Barcelona. This objective ensured a continuous stream of information, both internal and external, which enhanced the publicity of all BioStrength actions and achievements as well as of MBG publications that are specific for their research.

2. The acquisition of research equipment which was used:

• To advance MBG research to high-impact levels through upgrading infrastructure.
• To develop the high-end research unit/facility.
• To operate this unit/facility to the benefit of the MBG research groups as well as external - national and trans-national – users.

The unit/facility was named Cell Imaging and Biomolecular Interactions (CIBIT) unit and was based on the concept of core facilities with advanced technology. It was designed to be used both in house (as a research unit/facility) and in the region of Thrace or whole Greece (as a facility). The unit was equipped with two state-of-the-art instruments, a Laser Scaning Microscope (LSM) for detailed cell imaging and a Surface Plasmon Resonance (SPR) biosensor for the analysis of real-time biomolecular interactions. Software, computer control and smaller complementary instrumentation were also supported by BioStrength.

3. The enhancement of local expertise by recruiting experienced researchers who transferred to MBG scientific and technological expertise. The acquired expertise was used both holistically to boost the research projects of all MBG members and specifically to impart necessary knowledge and skills in order to promote and maintain a high-quality operational level of CIBIT facility. With respect to the CIBIT unit, since applying advanced technologies demands high expertise, it was proven extremely cost-effective to recruit for a defined period highly specialized and skilled personnel that serves as a “training seed” for local researchers.

4. The organization and participation in workshops. The workshops were targeted at specific training of MBG scientists as well as scientists at the national and international level and facilitating the exchange of scientific ideas. At the same time, the action promoted MBG’s international training capacity and reputation and gave a significant boost to knowledge sharing and networking.

5. Increased visibility of MBG and high public awareness about its actions via dissemination activities which targeted a wide audience, both in the scientific community and the general public. This objective ensured the publicity of all BioStrength actions and achievements as well as of MBG.

The proposed work plan was implemented through a set of five WPs, each describing the above work actions, plus an additional WP dedicated to project management. Total project duration was 36 months.


Project Results:
BioStrength's proposed plan was implemented through a set of five work packages (WPs) and an additional WP dedicated to project management:

WP1 Management and Co-ordination
WP2 Exchange of knowledge
WP3 Development and operation of CIBIT
WP4 Enhancement of knowledge by recruitment
WP5 Workshops and conferences
WP6 Dissemination Activities

The overall tasks of the project were split into two categories of actions: (a) those that relate to support activities (b) activities dealing with management issues. Category A included WP2, WP3, WP4, WP5 and WP6 and category B included WP1.

The Coordinator together with other members of the Project Management Board (PMB) have worked during project period in accordance to the schedule laid down in Annex I to providing management for the project and obtaining Deliverables, towards materialization of project objectives.


Management and Co-ordination (WP1)

All six WPs of BioStrength were carried out according to Annex I and produced Deliverables mostly at forecasted times, with the exception of only a few ones. A minor change in Annex I, upon Project Officer (PO) approval, was the consolidation of unconsumed resources at month 30 of the project to be used for the organization of another dual workshop not scheduled in the original Annex I (see WP5).

Project Management Board (PMB)
A PMB which is the main management body of the project was setup, consisting of:

1. Dr. Bogos (Pavlos) Agianian, Asst. Professor, Coordinator (WPL, WP1)
2. Dr. Katerina Chlichlia, Asst. Professor (WPL, WP2)
3. Dr. Giannoulis Fakis, Asst. Professor (WPL, WP5)
4. Dr. Maria Koffa, Asst. Professor (WPL, WP3)
5. Dr. Raphael Sandaltzopoulos, Accos. Professor (WPL, WP6)
6. Dr. George Skavdis, Asst. Professor (WPL, WP4)

Regular PMB meetings (once every 20 days on average) have been followed throughout. During these meetings, all issues associate to the project were discussed and decisions concerning management were taken, using the QMM. General assemblies of the project team members (MBG faculty) were taking place once every 6 months in which team members were briefed in detail about project progress, current status and future plans or when a major project decision (by vote) was necessary. More informal notes about specific actions were regularly delivered by the coordinator via email.

Kick-off Meeting
The project was launched at the kick-off meeting in Alexandroupolis on April 30th, 2009. During the meeting, a draft of the Quality Management Manual (QMM) and general management system was presented to team members and was agreed. The QMM was later finalized. The kick-off meeting attended the then Director General of General Secretariat for Research and Technology of Greece, Prof. F. Tsalidis as invited speaker, who expressed a very positive view for the project. On the same day preceding the assembly, talks were also given by steering board members and the coordinator. All talks were open to the public and were attended by numerous Democritus University of Thrace faculty and students.

Steering Board
According to Annex I, an advisory board was created. Members of the board were invited to attend the kick-off meeting. The Steering Board consisted of:

1. Dr. Rainer Pepperkok, Head, Advanced Light Microscopy Facility, EMBL-Heidelberg, Germany (Partner organization)
2. Dr. Jens Rietdorf, Head, Microscopy facility Friedrich Miescher Institute for Biomedical Research (FMI), Novartis, Basel, Switzerland (Partner organization)
3. Dr. John Pillmoor, Head, Technology Facility, University of York, UK (Partner organization)
5. Mr Makis Koutris (or representative), Head of Pharmaceutical Research, Pharmathen S.A. (Greek Pharmaceutical)
6. Dr Sissy Kolyva, EU Division, General Secretariat for Research and Technology of Greece.

Two Steering Committee meetings took place in Alexandroupolis in July, 2010 and February, 2012. Except Steering Committee members, the assembly attended PMB members and MBG faculty. On the same day preceding the assembly, talks were given by steering board members, the coordinator and senior scientists of CIBIT facility (WP4), which were open to the public and were attended by numerous Democritus University of Thrace faculty and students.

Management of Ethical Issues
An application for ethical approval was filed with Democritus University of Thrace Ethics Committee. Official approval was given since research on human genetic material, pathogens or other regulated biological material has not been conducted or was planned during the project.

Overall, almost all WP tasks and deliverables were according to schedule. Any deviation might be considered minor or anticipated in the Greek system, which is characterized by heavy administrative inflexibility and bureaucracy. Major milestones, with the most important one being the staffing and operation of CIBIT facility (WP3, WP4) have been accomplished with minor delays. A great success was the ability to attract scientists with strong scientific profiles (WP4), despite the apparent unattractiveness of Thrace. The facility is currently fully operational and a big number of internal projects were processed by its scientific personnel. Results were presented in conferences and published in scientific journals (WP6). Another important accomplished milestone was the very successful organization of international workshop during project duration (WP5). The secondment activities (WP2) were run smoothly and have contributed significantly to advancing the research potential of MBG faculty.


Exchange of knowledge (WP2)

The reinforcement of the research potential of MBG researcher groups was realized by:

1. Secondments of MBG researchers to partnering organizations where they had the opportunity to engage in research collaborations or consolidate partnerships, take part in research network building, have sabbatical time to write up and discuss results, exchange ideas, be exposed to emerging scientific trends and finally to get training in cutting-edge methods and techniques to the benefit of their own research plans. Training included technological areas or applications related to the Cell Imaging and Biomolecular Interaction (CIBIT) unit/facility (see WP3) in cases where these technologies were essential for current or future research projects. In parallel, research partnerships with SMEs or industries when this was essential to specific applied projects was encouraged. The secondments were not longer than two (2) months per MBG member over the time frame of BioStrength to ensure gain balance.

2. Inbound visits from experienced researchers and experts in strategic scientific fields related to the research that is carried over at MBG, CIBIT, or to future research implementations and plans. The visiting researchers exposed local faculty, staff and undergraduate/postgraduate students to the state-of-the-art in areas of their expertise, presented them innovations and trends, diffused advanced know-how and assisted in high-end technological integration. The scientists gave seminars, discussed and exchanged ideas and sparked novel routes in individual research.

Secondments of MBG researchers to partnering organizations, collaborative work with European research groups and attendance of meetings-conferences and workshops took place starting from June 2009. The majority of secondment time of MBG staff was consumed to participation/attendance of congresses/meetings and workshops, while many MBG faculty members moved to partner or non-partner organizations for collaborative research work or training to advanced methods. MBG researchers were exposed to emerging scientific trends and were trained in cutting-edge methods and techniques, transferring the obtained knowledge to the internal research structure. Seconded researchers offered internal tutorials and seminars and circulated printed and electronic material such as protocols, handbooks with technical tips, data analysis details etc. At the regional, national and European level, they propagated expertise to the scientific community by participating and instructing in workshops (WP5) organized by BioStrength, or other occasions, by teaching and by collaborative research.

Secondments to partner organizations were performed, while new host institutes of wider research interest were added. These included:

• The Advanced Light Microscopy Facility (ALMF) at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. ALMF is recognized internationally in the area of stat-of-the-art light microscopy and image analysis. The facility has a successful record of training in advanced methods in microscopy, confocal live cell imaging, high-throughput optical screening and data analysis.

• The Friedrich Miescher Institute (FMI) of Novartis Research Foundation, Basel, Switzerland. FMI is an internationally recognized research centre of high-excellence in biomedical research with a strong record of innovation in molecular biology. The Microscopy and Imaging core facility of FMI was willing to provide training and expertise on top-notch fluorescence microscopy and confocal cell imaging and to transfer knowledge on image acquisition and advanced image processing.

• The Centre for Genomic Regulation (CGR), Barcelona, Spain. CGR is an innovative center for basic and biomedical research. The Advanced Light Microscopy Unit of CGR was willing to be a technology transfer partner of MBG, advancing the effectiveness of CIBIT unit as well as the research potential of MBG as a whole.

• The Technology Facility of the Department of Biology, University of York, UK. This flagship facility transferred expertise and collaborated with individual MBG researchers on advanced molecular interactions and dynamics technologies, cell imaging and on several other areas including proteomics and analytical biochemistry, genomics and bioinformatics and protein production. The facility supported long-term research partnerships.

• The Department of Pharmacology at Oxford University, UK, is a 5* Department which is part of the Division of Medical Sciences. The department has world-leading support and training facilities and pursues advanced research programmes of high impact.

• The National Institute for Medical Research (NIMR), Mill Hill, London, UK. NIMR is a leading institute which performs world-class research in Genetics & Development, Infections and Immunity, Neurosciences and Structural Biology. The institute provided know-how, training and access to collaborations with various research groups.

• The EMBL-Hamburg outstation. EMBL-Hamburg is located on the site of DESY (German Synchrotron Research Centre) that provides synchrotron radiation (SR) through its DORIS positron storage ring. The outstation has a well-established record for the development of novel, innovative technologies in biological applications of SR and the use of integrated approaches to carry out scientifically demanding projects in structural biology.

• The Astbury Centre for Structural Molecular Biology (ACSMB) at the University of Leeds, UK, carries out high-quality research in all aspects of structural biology and has facilities specializing in the analysis of molecular interactions. It transfered knowledge on molecular interactions and Structural Molecular Biology.

• The Wellcome Trust Centre for Human Genetics (WTCHG) at University of Oxford, Oxford, UK. WTCHG is considered a leader in genomic research in Europe. The centre undertakes research into the genetic basis of multifactorial Human diseases. It is part of the University of Oxford's Division of Medical Sciences, with access to large patient collections and the Division’s considerable strengths in complex disease mapping.

• The MRC Research Complex at Harwell (RCaH), UK. RCaH is situated on the Rutherford Appleton Laboratory site adjacent to the Diamond Light Source, a new third generation synchrotron. Facilities used to study structure at the molecular level, including ISIS (the UK neutron spallation source), the Central Laser Facility (CLF) and the Biological Solid State NMR facility are on site. Other RCaH facilities included the MRC/BBSRC funded Oxford Protein Production Facility UK (OPPF-UK), the STFC Lasers for Science facility and the Electron Microscopy facility. The Collaborative Computational Project in Protein Crystallography (CCP4) is also be part of RCaH. RCaH provided the environment and facilities for researchers in the life and physical sciences to undertake research across traditional barriers.

• The Human Genetics Division at the Wellcome Trust Sanger Institute, at Hinxton, Cambridge, UK. The Sanger Institute is one of the leading genomics centers in the world, dedicated to analyzing and understanding genomes. Through large-scale analysis - and focused research and collaborations - the Sanger Institute's programmes underpin biological and medical research worldwide. Sanger Institute uses large-scale sequencing, informatics and analysis of genetic variation to further the understanding of gene function in health and disease and to generate data and resources of lasting value to biomedical research.

• The Proteomics Center at the Erasmus MC Centre for Biomics, Rotterdam, The Netherlands. The center provides mass spectrometry and proteomics services for the local scientific community, as well as for external researchers. The research projects in the laboratory are focused on the investigation of protein complex composition at different stages during the cell cycle and under different cellular conditions.

• The Institut de Science et d'Ingénierie Supramoléculaires, at Strasbourg, France. This institute is a world leader in supramolecular chemistry.

• The Food Microbiology Research Group (FMRG) and Microbiology and Biotechnology Research Group (MBRG), University of Ulster, N. Ireland, UK. FMRG, is a discrete research group within the Northern Ireland Centre for Diet and Health (NICHE) at the University of Ulster. NICHE was entered in the Biomedical Sciences unit of assessment and was awarded a 5* rating in the most recent UK Research Assessment Exercise.

New host institute Institut Jacques Monod in Paris-France, was added during the project. All secondments were less than two months long per MBG member in accordance to project description. MBG researchers had the opportunity to get training in advanced methodologies used in protein structure and function, modern molecular biology, genomic and cell biology research and greatly enhanced their research. Moreover these visits enhanced the existing collaborations and provided an opportunity for creating new ones at the visiting Institutes. The transfer of knowledge from the above mentioned Institutes maximized the opportunities of the researchers to use effectively the Laser Scanning Microscope and the SPR biosensor that were available at CIBIT facility (WP3), on applications that are specific for their research. Seconded researchers upon their return transfeerred their new research knowledge and technological expertise to their groups and other local researchers. Several seminars were given internally and internal discussions were organized.

This WP included a task of inbound visits of scholars to MBG. Seminars from experts in CiBIT’s technologies and visiting scientists, many of which were steering board members,were given. These were advertised to Democritus University of Thrace Departments and the wider public. Seminars during the kick-off Meeting and the Steering Committee meetings were open to the public. The prominent scientists, in addition to their seminars, were open to discussions with members of MBG and the recruited CiBIT scientists.

In another task of this WP, diffusion of knowledge, internal tutorials and seminars were held from all recruited senior and junior scientists. A material database of plasmids, E. coli strains, cell lines, secondary antibodies, research protocols and experimental procedures in electronic form was created and has been available to the members of the Department through BioStrength's website (www.biostrength.gr). The website was regularly updated with new information. CiBIT’s expertise on biomolecular interactions was propagated to the regional, national and European community through the operation of workshops. Electronic and printed material about the workshops were made available to MBG staff members and researchers. Moreover, internal workshops were held and repeated at certain intervals with the aim to increase internal knowledge and use of the facility. Internal workshops were organized by recruited scientists according to project related needs of researchers in order to provide problem-based training and solutions, boosting research at MBG. In addition, internal interaction between recruited scientists and researchers existed on a daily-basis.

Conclusively, the progress of the WP was continuous and on schedule. Overall activities of the work package advanced significantly the research potential of the Department of Molecular Biology & Genetics while the dissemination of knowledge accumulated major impact to internal research programs, increasing the competitiveness of the department for European research funding.


Development and operation of CIBIT facility (WP3)

A Cell Imaging and Biomolecular Interactions (CIBIT) facility unit was established. The main mission of CIBIT was to provide MBG and Democritus University of Thrace Alexandroupolis campus researchers with technologies and resources that will advance research projects, enhance in-house and external collaborations and support high-profile research. As MBG valued networking to be a pillar of European and regional development, the unit was scheduled to be open to regional, national and trans-national researchers, thus enhancing scientific collaboration, transfer of knowledge and the visibility of MBG. External usage was controlled on the basis of throughput and cost-effectiveness. Apart from BioStrength members, users included research groups from local Alexandroupolis University Hospital and in collaborations the commercial community (SMEs and industries).

Developing CIBIT unit necessitated purchasing two major instruments, a state-of-the-art Laser Scanning Microscope (LSM) and a Surface Plasmon Resonance (SPR) biosensor. These instruments and operation of CIBIT was supported by BioStrength and by MBG’s running budget. Redirection of complementary infrastructure currently at MBG according to an assessment of operational needs was performed on a regular basis.

The rational for the development of CIBIT unit was based on the realization of current trends in Molecular Biology and Biomedical research which characterize our post-genomic era which followed the resent explosion of data from major sequencing efforts, including the Human genome. Despite this genomics data bloom, many diseases related genes and gene products are poorly characterized. Given the fact that a reliable functional prediction of such products is currently weak, powerful methodologies are necessary to appreciate their biological, medicinal, biotechnological and biopharmaceutical context. A core part of these technologies are in vivo cell imaging and in vitro molecular interaction methods of study. The main S&T benefits for MBG to investing in building CIBIT unit are described below:

Cell Imaging
Unquestionably, light microscopy offers one of the most powerful tools for modern biological and medical proteomic research. In particular, the use of Green Fluorescent Protein (GFP) as a fusion marker, as well as the increasing availability of a broad range of other target-specific marker proteins in combination with new synthetic labelling dyes, has sparked the use by industry and academia of fluorescence imaging techniques. Current technology not only allows phenotypic analysis of tissue structure and cell morphology/mobility using contrast enhancing, but also enables the function, localization, dynamics, and interactions of specific cellular molecules within the context of the living cell to be observed and quantified. Such fluorescence-based technologies can be applied to research ranging from single cell/ single molecule approaches up to high throughput/ high content medicinal screens. The exacting demands of these applications are best and routinely addressed by the use of a laser based confocal system. In addition to offering per se much higher contrast and optical resolution, modern confocal microscopes have as standard the ability to perform advanced imaging especially suited to:

• Functional proteomics screens for the analysis of cell pathways in order to identify and characterise targets for drug discovery and medical diagnostics.

• Basic research studies of cell-based molecular function, interactions and dynamics. In particular Fluorescence Resonance Energy Transfer (FRET) having a range of 0 to 10 nm enables detection of direct molecular interactions and processes in cells.

• Spatial and temporal diffusion dynamics of macromolecules in the context of living cells, especially on cellular membranes, by photo-bleaching experiments such as FRAP (Fluorescence Recovery after Photo-Bleaching) and FLIP (Fluorescence Loss in Photo-bleaching). Furthermore, due to its highly modular construction a modern confocal microscope can acquire additional capabilities such as FCS (Fluorescence Correlation Spectroscopy) or FLIM (Fluorescence Lifetime Imaging Microscopy).

CIBIT facility was equipped with a Laser Scaning Microscope (LSM) based on an Andor Revolution Spinning Disk Confocal System, which has an Olympus IX81 inverted fluorescence microscope base, a Prior motorized XY stage H117, a Prior NanoScan Z piezo-based z-drive, a Yokogawa CSU X-1 scan head, an Andor IxonEM+885 camera, FRAP-PA and TIRF modules and a customized laser combiner. The confocal system is supported with an environmental control box with CO2 line for live cell microscopy. Operation of the system is controlled using imaging software packages: Andor IQ 1.10.3 and IQ 2.0. The microscopy unit is state-of-the art and unique in Greece with the capability to perform the following analyses on cells and biological samples with medical importance:

• Confocal / widefield / TIRF imaging
• Imaging of fixed and living samples
• Multi-color imaging
• Z-sectioning
• Multi position / multi field imaging
• Field scan imaging
• Time course imaging
• FRAP (Fluorescence Recovery After Photo-Bleaching)
• FRET (Fluorescence Resonance Energy Transfer) by sensitized emission or acceptor photo-bleaching
• FLIP (Fluorescence Loss In Photo-Bleaching)
• PALM (Photo-Activated Localization Microscopy, under development)


Biomolecular Interactions
The ability to study molecular interactions in vitro is essential and complementary to cell imaging and grasps on the fact that such studies are often simpler to interpret, better controlled and cost-effective. We aimed to advance research in molecular interactions of proteins and other biomolecules that drive and regulate biological processes to supreme levels by purchasing a versatile SPR biosensor which records real time binding data. This technology can be used to study a wide range of bio-effectors including proteins, DNA/RNA, carbohydrates/lipids and whole cells, viruses or bacteria in the context of many potential applications:

• Defining the characteristics of biomolecular interactions in elucidating disease mechanisms, thermodynamic and kinetic profiles, multiplexed interaction analyses and in deciding on potential drug targets and diagnostic markers.
• Label-free screening of macromolecular and drug-target interactions, providing data on binding selectivity/affinity/thermodynamics, SAR/QSAR , ranking of targets and early ADME indications. Specific target identification can be performed by linking to MALDI proteomic analysis.
• Understanding biological processes at the molecular level, e.g. defining structure/function relationships and realizing the dynamics of molecular pathways.
• In Biotherapeutics, in particular detecting and characterizing the affinity, specificity and kinetics of immune responses by antibody and antibody fragment binding and epitope mapping or measuring immunogenicity during vaccine/immunotherapeutic development and pharmacodynamics.
• Selecting better research tools based on variation in functional binding properties of biomolecules.

CIBIT facility was equipped with the ProteOn XPR36 (Bio-Rad) state of the art surface plasmon resonance biosensor. The system has been used to study interactions of molecules of biological and medical importance. Molecular interactions are dynamic processes and as such require real time measurements in order to accurately determine kinetic parameters. Employment of the principle of surface plasmon resonance (SPR) provides real time monitoring of binding and dissociation of partner molecules and is well suited to this demand compared to end-point techniques. SPR biosensors consume small amounts of sample. Sample labeling is not required thus analysis of relatively native molecules is a plus. To study the interaction between two molecules, one is first injected and bound on the gold coated chip surface (ligand) and the other is injected and flown over the ligand bound surface (analyte) through microfluidic channels. Interaction causes mass accumulation on the chip surface which is sensed/detected as a change of the SPR angle. Acquired data (response units, RU) vs time are collected and displayed in real time on a sensorgram providing quantitative information on binding specificity, stoichiometry, concentration, kinetics (ka, kd) and overall affinity (KD=kd/ka).

Advanced S&T features of the ProteOn XPR36 instrument include:

-a total of 36 interaction spots per chip allowing the analysis of equal interactions in a single run. These interaction spots consist of a 2-dimension array 6x6. In one dimension the six parallel flow channels may be used to immobilize strips of six targets (ligands) on the sensor surface. This high throughput assembly is advantageous for antibody or drug/small molecule screening.

- internal referencing option by utilization of reference spots automatically formed before and after each reaction spot which may be complemented by the use of 1 of 6 ligand flow channel as an additional reference surface providing a thorough referencing system. It should be mentioned that improved referencing allows more accurate determination of kinetic parameters.

Both the above features are advantageous due to overall time and reagents saving for the experimental setting since the ability to complete the experiment in a single run diminishes the need for regeneration of the chip surface. Regeneration of the chip surface (i.e. stripping off bound analyte), a necessary procedure if reuse of the chip in a new experiment is desired, may modify the chip surface introducing artifacts in the comparison of data sets obtained before and after a round of regeneration.

Most commonly protein interactions analyzed by the SPR system in CIBIT was:

1. Protein-protein including but not limited to antibody-antigen interactions (antibody screening, epitope mapping, determination of cross-reactivity of antibodies used in multiple assays.
2. Protein-DNA/RNA interactions, in particular using biotilynated oligonucleotides.
3. Protein-small molecule (minimum molecular weight 200 Da) interactions for analysis of enzyme-inhibitor interactions (drug/small molecule screening) and ligand-receptor interactions.

Through the establishment of CIBIT facility, MBG enhanced not only the research potential of its faculty teams via performin high-quality competitive research, but also provided service to local and national research groups enhancing collaborations between academic groups and industry. To support the operation of the unit, experienced scientists were recruited (WP4). The facility has served 2/3 of the MBG faculty members, has produced international publications and has created a basis for successful national and EU research proposals and research collaborations.

An international measure of CIBIT's success is reflected in two recent accomplishments: a) the Cell Imaging unit has been chosen to serve as a European proof-of-concept test side under FP7-ESFRI EUROBIOIMAGING consortium (Nature, 2011, 477, 523) for the period Jan-July 2012 and b) the Biomolecular Interactions unit has been invited to participate in an worldwide SPR global benchmark study organized by the Center of Biomolecular Interaction Analysis university of Utah, USA. Additionally, the establishment and operation of the imaging unit was a catalyst in succeeding to attract the 11th ELMI meeting, the flagship European microcopy meeting, in Alexandroupolis which took place on 7-10 June 2011. The meeting was co-organized by CiBIT and was an excellent opportunity to demonstrate CiBIT’s imaging capacity to a wide international community of microcopists. The feedback MBG received from these scientists was extremely positive.



Enhancement of knowledge by recruitment (WP4)

To enhance the research capacity of MBG, two senior researchers and two young scientists were recruited, who supported the operation of CiBIT facility, bringing fresh ideas and technological expertise. Know-how and experience was transferred through several activities including seminars and internal as well as external workshops. Selection of applicants was based on research excellence, technical expertise, publication records and past scientific achievements.

Five person-years of senior experienced researchers were associated with operation of CIBIT. Two and a half of the five person-years were dedicated to supporting Cell Imaging while the other two and a half years were used to support Biomolecular Interactions. Recruited senior researchers had experience in the support of core facilities or significant postdoctoral experience in relevant to CIBIT research, or past association with related industrial units.

The researchers were involved in the day to day operation of CIBIT and in:

• Setting-up advanced methods and protocols
• Adjusting, maintaining and fine-tuning equipment as required
• Providing support to external users
• Performing research
• Transferring their knowledge locally in regular training sessions and externally in conferences
• Supporting the organization of, and instructing in, BioStrength workshops (WP5) and writing reports, among others.

Four person-years of BioStrength were initially scheduled to recruit young scientists with a PhD/Master degree or equivalent experience. Almost two and a half years were consumed because one of the junior scientists exited the project due to maternal leave. The junior scientists were actively involved in research plans of MBG faculty that included:

• Projects that take direct advantage of the opportunities opened by implementation of CIBIT technological platform and projects which develop the S&T capacity of MBG.
• Advancement of high-risk or high-end research projects which are anticipated to radically advance MBG’s research record and reputation.
• Collaborations between MBG faculty and outstanding external research groups, including groups from interested SMEs or industries.

The following scientists were hired:

For the senior scientist positions:
1. Dr. Girod Andreas
2. Dr. Pavlaki Maria

For the young scientist positions:
1. Dr. Drosou Vasiliki
2. Dr. Kalamida Maria

CVs of the 4 recruited CiBIT scientists can be found at BioStrength’s website www.biostrength.gr

The above mentioned scientists have worked productively over the years to make CiBIT fully operational and they have organized and instructed in series of internal training events and 3 international workshops (WP5). Furthermore they initiated several fruitful collaborations with MBG scientists and appear as co-authors in publications. Results from these collaborations have been published in National and International conference abstracts and poster presentations as wells as peer reviewed scientific journals (WP6). Apart from these conference abstracts, recruited scientists have given several seminars.


Workshops and conferences (WP5)

A. Hands-on workshops
Two hands-on workshops were initially planed to be held during the second and third year of the project as well as an International Conference. Upon PO approval, and due to the success of organized workshops and their significance for Democritus University and the region of Thrace, unconsumed resources from one junior position (see WP4), the cost for the International Conference and inbound visits (WP2) were consolidated and used to organize a third, dual, local workshop towards the end of the project.

The organized workshops were:

1. International workshop on BIOMOLECULAR INTERACTIONS held 11-14 October, 2010 at CIBIT facility MBG, Alexandroupolis, Greece

2. International workshop on CELL IMAGING AND ANALYSIS, held 2 - 6 October, 2011 at CIBIT facility MBG, Alexandroupolis, Greece

3. Dual workshop on CONFOCAL IMAGING IN THE BIOMEDICINE and BIOMOLECULAR INTERACTIONS IN THE CLINICAL PRACTICE, held 20-21 February, 2012 at CIBIT facility MBG, Alexandroupolis, Greece.

MBG faculty members, CIBIT scientists together with WP leaders and the coordinator constituted scientific organizing committees for each workshop to deal with all issues related to workshop planning, management, organization and realization. The scientific committees organized the scientific and day programme, determined the topics of the lectures and worked towards realization of the workshop. Moreover, it was decided that the workshops will be hands-on, so that the technological aspects of CIBIT are clearly disseminated to the scientific community. The committees met several times and created a complete planning to each workshop related WP5 tasks. The coordinator, Dr Bogos (Pavlos) Agianian, participated in many of these meetings, providing scientific and managerial assistance.

Open calls to receiving trainee applications were widely publicized (WP6). Supporting cross-disciplinarity, applications from postgraduates and young scientists from the Balkan region and Europe were particularly encouraged. Workshop application were online, with applicants noting their CV and statements of past research and expectations from the course. Successful workshop applicants were selected by the scientific organizing committees and were presented to the BioStrength team. An important criterion for the selection was the relevance of the candidate’s research interests and current work to the course objectives, in order to maximize scientific gain at individual career point. The committees decided that the theme of the first two workshops would be on Cell Imaging and Biomolecular Analysis via SPR, the main scientific areas developed by CIBIT. The third workshop which was a results of project amendment, was targeted to local and internal trainees, aiming at:

1. Maximizing the research potential and visibility of MBG by enhancing training interactions with scientists from regional Medical School of Democritus University of Thrace, other Greek universities and research centers and SME/industrial collaborators. The interaction had a particular impact on creating new and extending past strong collaborations with the Medical Department, resulting in joint grant proposals and patent prospects. In addition, the research capacity of MBG graduates and other junior Greek researchers could be positively affected, as they could implement the specialized knowledge acquired to their research plans, and, at the same time, advance their career prospects.
2. Allowing CiBIT facility to tune-up its know-how and expertise to suit international commitments, including i) serving as a proof of principle confocal imaging testing site under FP7-ESFRI project EUPOBIOIMAGING and ii) serving as an international SPR data quality assessment site in collaboration with the University of Utah, USA . Both activities are active and operate at the highest scientific standards providing unprecedented international recognition to MBG and DUTH and .
3. Fortifying CiBIT as a clearly recognizable facility with unique training and research reputation in the Greek scientific community. CIBIT is the only facility with such advanced capacities in the area of molecular interactions (Surface Plasmon Resonance) and bio-imaging (spinning disc confocal microscopy) in North Greece, a geographical region of almost 3 million inhabitants and home to several industries and universities. MBG is planning to sustain this superior capacity by implementing a Masters program on “Biomedical Applications”.

For the workshop on BIOMOLECULAR INTERACTIONS the majority of applications were from Greek labs. A total of 8 external trainees were selected, 7 originating from Greek institutions (including an applicant from a Greek biotech SME) and 1 from the UK (Oxford U.). An additional 4 MBG post-graduate students were included, after a recommendation from the PMB. Therefore the total trainee number was 12. In addition to MBG faculty members, four external scientists of international caliber and one PhD from sponsoring company Bio-Rad Hellas instructed the workshop.
The course taught practical and theoretical aspects of Biomolecular Interactions analysis, with practical sessions covering protein-protein and protein-drug interactions using Surface Plasmon Resonance (SPR) and Differential Scanning Fluorimetry (DSF). The theoretical part of the course provided background knowledge on microcalorimetry (ITC/DSC), proteomics, spectroscopic methods (NMR, CD) and the analysis of SPR and DSF data.

The instructors/speakers team consisted of:
1. Dr Alexander Fish, NKI-Amsterdam, The Netherlands
2. Dr Vladimir Rybin, EMBL-Heidelberg, Germany
3. Dr George Panayotou, A. Fleming Institute-Athens, Greece
4. Dr Anastasia Politou, Medical Department-Ioannina, Greece
5. Dr Serafeimoula Gkritzapi, Bio-Rad Hellas, Greece (sponsoring company)
6. Dr Maria Pavlaki, CIBIT
7. Dr Victoria Drossou, CIBIT
8. Dr Dimitra Kalamida, CIBIT
9. Dr Bogos (Pavlos) Agianian, MBG, Coordinator BioStrength
10. Dr Katerina Katsani, MBG

The practical workshop on CELL IMAGING AND ANALYSIS was attended by 12 external trainees (6 from Greece, 6 international) and 6 external instructors. The international trainees were from the UK (Oxford University), Cyprus (University of Cyprus) and Hungary (University of Debrecen). A number of MBG post-graduate students, after recommendation from the PMB, followed practical sessions of the workshop.
The topics of the workshop were on Wide field microscopy, Spinning disk confocal microscopy, Line scanning confocal microscopy, Live cell imaging, Fluorescence Recovery After Photo-Bleaching (FRAP), Fluorescence Resonance Energy Transfer (FRET), Data analysis / Image processing (ImageJ, FIJI), Image deconvolution (Huygens) and Sample preparation

The instructors/speakers team consisted of:

1. Dr. Michael Doube, MPI Dresden, Germany
2. Dr. Spyros Georgatos, U. Ioannina, Greece
3. Dr. Vasso Kostourou, BSRC, Athens, Greece
4. Dr. Yilmaz Niyaz, Zeiss Europe, Germany (sponsoring company)
5. Dr. Vincent Schoonderwoet, SVI, The Netherlands (sponsoring company)
6. Dr. Britta Schroth-Diez, MPI Dresden, Germany
7. Dr. Andreas Girod, CIBIT
8. Dr Dimitra Kalamida, CIBIT
9. Dr. Maria Koffa, MBG

The dual workshop on CONFOCAL IMAGING IN THE BIOMEDICINE and BIOMOLECULAR INTERACTIONS IN THE CLINICAL PRACTICE was mainly focused to local trainees from the Medical Department of Democritus University of Thrace and University Hospital at Alexandroupolis as wells as MBG postdocs and graduate students. The workshop was attended by 18 trainees, all from MBG, the Medical School of Democritus University of Thrace and the Alexandroupolis University Hospital. All lectures and talks were open to the public and students at all levels. All CIBIT scientists instructed the workshop.

A locally recruited IT technical expert worked for the software and IT support of the workshops. Recruited researchers/scientists (WP4) with relevant know-how participated actively in all hands-on training sessions. Lectures supporting the theoretical part of the workshops were provided by CIBIT members, participating MBG faculty and by the external instructors and speakers. A typical workshop day included one morning and one afternoon training session, each consisting of theory presentations and one practical. The presentations of each session was scheduled so that it provided a comprehensive theoretical background to the subsequent practical. Each workshop incorporated keynote lectures on topics of profound scientific interest related to the theme of the workshop, given by scientifically prominent invited instructors. All instructors were involved in the evaluation progress of trainees and in assessing trainee evaluation reports.

During duration of each workshop there were social events apart from the intensive theory and training programme which encouraged networking and the exchange of scientific ideas. Full cost for travel and accommodation for workshop instructors was covered by BioStrength as well as the cost of catering for the events. MBG did not charge bench fees or overheads to workshop participants.
In all workshops, training sessions were designed to address real applications of the methods in the biomedical sciences, molecular medicine, biotechnology, pharmacodynamics or other applied areas that contributed to further widen the scientific capacity of trainees as well as of MBG and CIBIT facility.

All workshops were evaluated by trainees and indeed external instructors extremely favorable. Analysis of evaluation slips in the categories, a) quality of scientific talks, b) course programme, c) facilities, instructors knowledge, d) training material and e) organization, showed a minimum of 85% of trainees giving an "Excellent" or "Very Good" mark in all categories.


B. International short-term training and meetings/conferences
MBG researchers took part in short-term training and participated at international scientific conferences under this WP. Short-term training was in national and international laboratories, hands-on workshops or similar training activities. Participating researchers upon their return to MBG conveyed knowledge locally through seminars or practical demonstrations when appropriate. The BioStrength funds allocated for international training or meeting/conference time covered the cost of fees, travel, boarding and other associated expenses. This action was in concurrence and acted supplementary to WP2.


Dissemination Activities (WP6)

A website (www.biostrength.gr) was designed and developed, featuring detailed information on the actions, research, services, workshops and conference, contact information and all other relevant topics of BioStrength. An IT company in Thrace (INFORMATICA SA) was selected to support the website. The website has currently received more than 11000 hits from 85 countries! Importantly, 75% of the visitors are from countries other than Greece. The web site has served as an efficient means of advertisement for the workshops (WP5) and all related application documents were downloadable from the site. Sections of the website have restricted access only to members associated to the project for the exchange of internal information. The site is an effective way of communication for CiBIT’s users and personnel as well as MBG researchers. In addition, it serves as a platform for the organized electronic deposit and storage of protocols and lists of molecular tools (plasmids, bacterial strains, cell lines, antibodies, etc. see WP3) available to MBG from CIBIT. This collaborative platform enhances synergies and promotes collaborations among the members of the faculty and other researchers, while cost economy is achieved.

Printed or electronic material such as posters, brochures and flyers were used to present MBGs research potential and CIBIT facility and attract interest of researchers and potential users as well as advertise workshops to potential participants. Such material was also used to disseminate MBG’s research achievements. The material was emailed and posted to selected EU Research Institutes/Centres and Universities and to research/educational institutions in neighboring EU and non-EU Balkan countries. The material was also available on BioStrength website.

Printed material connected to project dissemination has been produced as follows:

1. Kick-off meeting (April 30th, 2009): Leaflet with schedule, Invitation cards and Poster sent by post to Democritus University of Thrace and local political authorities. The event was covered by two local TV channels.
2. Steering-committee meetings (July 2010, Feb 2012). The scientific portion of these meetings was open to the public. Leaflet with programme was sent by emails to Democritus University of Thrace and MBG members.
3. A brochure designed to present and promote CIBIT facility. This brochure has been sent to numerous Universities, Research Institutes, Scientific Societies and individual researchers in Greece and abroad. It was also included in the advertising material of all workshops (WP5).
4. Color posters advertising the workshops. Further advertisement was via the website and e-mails.
5. Posters advertising inbound talks and internal seminars from recruited scientists (WP4) sent by emails.
6. Scientific results generated in CiBIT unit have been presented in numerous scientific meeting and conferences in Greece and abroad, clearly acknowledging the contribution of CIBIT unit in obtaining results.

Workbooks and selected protocols supporting users of the CIBIT unit (WP3) as well as workshops (WP5) were distributed electronically. Manuscripts related to BioStrength have also been published in international peer reviewed journals. In all visibility and dissemination actions, in paper or electronic at national and international press, conferences/meeting, journals or any other occasion included acknowledgement of funding and support by the European Commission according to the mandate of EC directorate 1159/2000.

Finally, these promotional materials and actions helped to incite new collaborations with Greek research centers and European research institutions and to become more competitive for future European grant funding.

Potential Impact:
MBG has a vision for its strategic research role primarily in Greece and the Balkans as well as the rest of Europe that requires resources which exceed contributions allocated to it from the National RTD budget, currently the lowest in the EU-15. MBG plans to maintain and further invest in its human potential - which has successfully attained the necessary critical mass of research expertise and technology - and in its infrastructure in order to compete for European research funds and achieve the long-term goals that it has set. MBG intends to fully exploit two more of its unique attributes:

• It is the only University Department in Greece that provides an undergraduate curriculum dedicated to Molecular Biology and Genetics.
• Its faculty is young, well trained and with international experience in research centers and Organizations among the best in Europe and the World

BioStrength was compiled and executed following this strategic framework of MBG. The success of the project relied on the orchestrated co-ordination of Human resources and infrastructure that it proposed. Accomplishment of project objectives provided considerable impact towards development of:

• The S&T capacity of MBG and the quality of individual, group and collaborative research.
• Long-lasting partnerships and twining with centres of research excellence towards the concrete integration into the European research charter.
• The strategic placement of MBG into European research players improving critically its capacity to participate in FP7 projects and networks.
• The regional and European R&D and the economic and social cohesion.

Further analysis of the specific impacts expected from successful completion of BioStrength follows:

Excelling Research capacity and capability
BioStrength objectives were directly related to S&T enhancement of the project team and MBG as a whole. In particular, the specific implementation axes via which BioStrength upgraded the RTD capacity of MBG were:

1. The significant enhancement in individual S&T and peer-reviewed research impact for each member of MBG by the BioStrength project in its entirety, in particular by access to CIBIT unit, trans-national two-way secondments (WP2), re-enforcement and mobilization of Human potential with external highly skilled researchers (WP4) and a strong programme of external short-term training on state-of-the-art methods and technologies (WP5).

2. The restructuring of infrastructure and complementarity with new research equipment from CIBIT (see WP3). This step brought a significant advancement in the research structuring at MBG as all faculty members had access to valuable multidisciplinary technologies to the benefit of individual researchers and teams. This resulted in coherent advancements in know-how and methods that were fragmented at MBG and increased both the quality and impact of scientific studies and the synergy between MBG faculty members and other Greek scientists. CIBIT’s technologies was essential to advance in-house projects on the mechanisms of major human diseases like cancer and diabetes while at the same time opened up the possibility to engage in biotherapeutic research, medical molecular biology and genetics and other relevant areas. At the same time CIBIT unit has been an important asset for MBG that can develop into an attractive Greek and Balkan Centre of advanced cell imaging and biomolecular analysis.

3. An effective boost to MBG’s research reputation and attractiveness through the interaction with external users of CIBIT unit from the regional, National or trans-national research community. Local academic users included the Medical School of DPTH which is situated in Alexandroupolis and with which MBG has on-going research collaborations. With regards to the Medical School of DPTH which has a wide and solid scientific background, partnership with MBG and cross-departmental collaboration is critical to acquire a competitive-edge in the biomedicinal area with impact in the Balkans and wider. It should be noted that only a very small number of services in the scientific themes advanced in CIBIT that are open to external users exist in Greece, and none in the region of East Macedonia & Thrace.

4. A significant boost in training capacity of MBG faculty through their involvement in practical workshops (WP5) which will be used as an asset to sustaining strong in-group knowledge-transfer flows, attraction of highly qualified students and a better management of individual research groups to increase productivity, quality and cost-effectiveness.


Enhancing integration in the ERA
BioStrength was highly integrative with respect to European partnership and beyond:

• Through WP2, MBG developed sustainable partnerships with distinguished RTD centers. The two-way secondments of researchers enhanced the trans-national character of MBG and connected it to some of the best European research and training centers providing a unique opportunity to enhance the potential for collaborations, scientific breakthroughs and technological advances. These brain-gain activities have already created long-lasting strategic partnerships with the receiving organizations that extent beyond the time framework of BioStrength.

• Through WP3 (CIBIT unit), solid contacts with academic and commercial sponsors were established which strengthened both basic and applied research. These interactions promoted an interest in targeted research which may create exploitable patents and provoke the establishment of spin-offs, improving MBG’s competitiveness in actions that require commercial participation.

• The recruitment of experienced researchers (WP4) further reinforced contacts with European research and sustained a track of knowledge-exchange and increased accessibility.

• Through WP5, BioStrength fostered multi-national scientific interactions in the form of workshops and supported high-impact short-term training and networking. Collectively, WP2 and WP5 supported directly and decisively MBG’s integration in the European Research Area.

• Through WP6, MBG capitalized visibility actions and upgraded its status from a small department of a convergent European region to a noticeable regional centre in Greece, the Balkans and SE Europe. At the same time, research publications including results obtained in CIBIT cemented scientific reputation and status in the pan-European research community.

Overall, the working plan of BioStrength ensured a high degree of integrative networking that promoted and is expected to maintain MBG’s plans to carry research way beyond its current limits of know-how and infrastructure. In addition to these points, BioStrength was coherent to the following EU policies towards strengthening European research integration:

• The EU policy for an information and knowledge-based society, stressing the need to encompass the emerging technological revolution and change in the exchange of knowledge affecting all institutions and aspects of the society (European Council, Lisbon, 2000)

• The EU policy on research which aims to bring national and EU endeavours together through networking and co-operation and to build a research and innovation equivalent of the “common market" for goods and services.


Improving the capacity to participate in FP7 projects
Most MBG faculty members have just passed the starting up stage of their academic careers and are vibrant independent researchers with significant potential to deliver S&T objectives in the area of Molecular Biology and Genetics of considerable impact to SE Europe and beyond. National resources appear inadequate or fragmented especially with respect to the immense investment in infrastructure, development of know-how and Human resources required to carry out competitive high-impact research in contemporary themes of Molecular Biology or Genetics. BioStrength, incurred immediate advancement in all above prerequisites and was critical in fully developing individual research capacities, career paths and overall research capacity of MBG. Enforcement of these merits through BioStrength, improved MBG's capacity to participate in FP7 activities for the following reasons:

• The advancement in know-how, especially from European knowledge centers, related to WP2, WP4 and WP5 was crucial in upgrading the quality of current research projects, thus enhancing the potential to compete for European funds. In parallel, induced scientific collaborations with partner organizations (WP2) and networking (WP2, WP5) strengthened the participation of MBG research groups in European networks.
• The interaction with SMEs and industries, through workshop sponsoring (WP5) and participation in project's Steering Committee (WP1) advanced managing skills and positioned MBG favorably to attract EU funds related to research and development and commercialization.
• The development of the high-end research facility CIBIT (WP3), maintained a long-lasting resource for the attraction of collaborators and users, further enhancing the potential for participation in FP7 networks.
• The increased visibility of MBG, a corollary of workshops and dissemination actions (WP5, WP6), incited potential in-coming partners to assemble co-operations with MBG. These actions guaranteed feedback from the research community and the pubic which improved MBG’s experience as a research player in Europe.
• The completion of BioStrength, a major 36 month project, precipitated knowledge on managing and running European grants, a valuable asset for future grant applications.


Improving regional capacity building and socio-economic cohesion
As already outlined, MBG seeks to become a regional center of excellence for research and training. Simultaneously, MBG seeks to increase its impact and establish such a position in the European and the National RTD charter that will bring considerable benefits from regional cohesion policies (through the European Regional Development Fund), in which Greece is a beneficiary, or influences these policies. This target will be strengthened by the utilization of regional and national cohesion policies, which are substantially supported by Greek programms like the National Strategic Development Plan (NSDP) and Regional Operating Programme (ROP).

The short-term economic impact of BioStrength is not immediate but the project will be of value in the middle- and long-term in responding to regional socio-economic needs. The regional socio-economic impact of BioStrength can be detailed as follows:

1. Although Thrace is a typical convergence region, the demand in innovation and technological commercialization increases steadily. Many aspects of BioStrength, especially the CIBIT unit, may result in patents and scientific breakthroughs with an immediate interest to the market. Several MBG investigators have been co-authors in successful patent applications and a critical few have extensive experience in the bio-industrial sector.
The impact of BioStrength’s activities to the regional and National commercial sector can be substantial and is summarized as follows:
• Thrace currently has one major pharmaceutical industry unit, Pharmathen SA, which maintains an aggressive export character. BioStrength's implementation allowed strong contacts with Pharmathen SA as executive members of the company were members of BioStrength's Steering Committee.
Technology-transfer via CIBIT unit can support jointed S&T projects in the areas of toxicology studies and pharmacology screens, preclinical trials, biotherapeutics, medical and diagnostic proteomics and many other. These possibilities are currently explored.
• CIBIT has created the S&T platform which can create exploitable patents from results of collaborative research between SMEs/Industries and MBG.
• BioStrength advanced MBG expertise for development of S&T programmes that can create SMEs or spin-offs.
• The international workshops promoted contacts with sponsoring companies and boosted joined research.

2. The demand in competent researchers and science-related managers is also expected to rise sharply both in the region of East Macedonia and Thrace and in Greece overall. Implementation of BioStrength via workshops (WP5) trained Greek scientists and local students interested to work in the bio-sector. It also enhanced training and networking with researchers from other countries. The transfer of knowledge and its application in developing R&D programmes by these trained individuals is expected to improve the socio-economic environment of the region.
3. The major societal impact of BioStrength lies in its contribution to change the current established concept about R&D in Thrace and promote a regional social consciousness about S&T actions which is currently extremely weak. This was realized by the local society via dissemination actions (WP6) which included open to the public kick-off and Steering Committee meetings. These activities also shaped ethical views on research in the bio-sciences and contribute to place these views in their correct scientific perspective.

It should be noted that BioStrength promoted employment of regional researchers. This was achieved in the case of the project secretary (WP1), IT technical expert for workshop support (WP5) and the website (WP6). This is coherent to the European strategy on employment as it is expressed in the Lisbon Agenda which seeks to turn Europe into a competitive and dynamic knowledge-driven economy. BioStrength also conformed to European employment policies focusing on increasing employment in services and extending all aspects of equal opportunities, including reducing occupational segregation.


Spreading excellence and Disseminating knowledge
Dissemination of research milestones and results to other researchers and other stakeholders represented a key activity in BioStrength. The spreading of excellence produced from BioStrength proceeded via different dissemination routes:

• Internally: Between MBG members and staff and across the Democritus University of Thrace campus using BioStrength’s website (WP6), internal seminars (WP2, WP4), steering meetings and member general assemblies (WP1). Also via e-mails, electronic newsletters, reports and presentations by invited scientists and by recruited researchers.

• Externally: (1) To researchers outside MBG and the Democritus University of Thrace was achieved via the public domain of BioStrength website, via publications in international peer-reviewed journals, participation in workshops and national as well as international scientific meetings and conferences and BioStrength’s workshops (WP5). (2) To National and International research centers having similar or related scientific interests, mediated mainly via BioStrength’s website as well as direct communication. Many of the instructors of organized workshops (WP5) were attracted via this route (3) To the industry and commercial companies via CIBIT's training activities and inclusion of regional industry in the Steering Committee(WP1) (4) To the healthcare sector, in particular Alexandroupolis Hospital and Medical School via local training organized by CIBIT (WP5) and by seminars (WP2, WP5) (5) To the society and the broader public through BioStrength’s website, press releases, publications and the organization of Open Days which were combined to Steering Committee meetings.

Strong publicity, which was not predicted in Annex I, was provided by the facts that a) the Cell Imaging unit of CIBIT has been chosen to serve as a European proof-of-concept test side under FP7-ESFRI EUROBIOIMAGING consortium as published in Nature, 2011, 477, 523 and b) the Biomolecular Interactions unit has been invited to participate in an worldwide SPR global benchmark study organized by the Center of Biomolecular Interaction Analysis university of Utah, USA. Additionally, the establishment and operation of Cell Imaging unit of CIBIT was a catalyst in succeeding to attract the 11th ELMI meeting, the flagship European microcopy meeting, in Alexandroupolis which took place on 7-10 June 2011. This major international meeting provided high publicity to BioStrength project and MBG.

Overall, the endeavors envisaged in BioStrength elevated research potential and were instrumental to attracting further R&D funds and sustain a strong presence in the European research community, establishing MBG into an emerging regional center of excellence with increased impact to socio-economic development.


Exploiting results
The research carried out as a result of BioStrength’s implementation resulted in publications in peer-reviewed international journals, reports to the scientific community and may potentially result in patents. Interaction with industries and SMEs was mediated in two main occasions:

1. Sponsoring of BioStrength organized workshops. Companies included Bio-Rad Hellas (GR), Interlab SA (GR), SVI (NL), Andor (DE) and Zeiss (DE). A strong prospect for collaboration with some of these companies has been created through this interaction. In particular, Bio-Rad Ltd is discussing the possibility to develop SPR detection kits jointly with CIBIT, and Andor to provide know-how in microscopy.
2. The participation of local pharmaceutical company Pharmathen SA in BioStrength's steering committee. This interaction facilitated submission and funding of joined research grants with members of MBG. Exploitation of results may result in jointed patent applications.

Any Intellectual Property (IP) management issues concerning technology transfer will be managed by the Technology Transfer Office of Democritus University of Thrace, including potential commercial exploitation of scientific results. Patent applications will comply with European Patent Law and National legal procedures. Legal issues will be managed by the Legal Counsel of Democritus University of Thrace.

List of Websites:
Websites:
www.biostrength.gr
www.mbg.duth.gr

CIBIT:
Department of Molecular Biology & Genetics
Democritus University of Thace
68100 Alexandroupolis
E-mail: cibit@mbg.duth.gr

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