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Opening doors to excellence. Enabling OMICs high-thROughput techNologies at the Faculty of Medicine Jagiellonian University Medical College

Final Report Summary - OMICRON (Opening doors to excellence. Enabling OMICs high-thROughput techNologies at the Faculty of Medicine Jagiellonian University Medical College)

Executive Summary:
The REGPOT project “Opening doors to excellence. Enabling OMICs high-thROughput techNologies at the Faculty of Medicine Jagiellonian University Medical College”, acronym OMICRON.

The aims of the Final Report are to show a wide audience the final results of OMICRON Project, summarizing the major achievements and impacts as well as:
1. the extent to which the OMICRON Project has been successful in achieving its objectives and those of the REGPOT Programme;
2. the impacts that the project has had on the host, Jagiellonian University Medical College (JUMC), the Malopolska region, and the employees of OMICRON; and
3. the opportunities and challenges facing the future development of the Centre for Medical Genomics – OMICRON (the OMICRON Centre).

The report shows that the progress made within OMICRON Project has already had a significant impact on the OMICRON Centre and JUMC, as well as on the local and the international scientific community. The project has allowed students and post-doctoral fellows to interact with researchers of international recognition and has fostered long-term collaborations, which have been supported through exchanges with excellent institutes. The extensive and advanced research projects already undertaken and ongoing in the OMICRON Project have established the OMICRON Centre and JUMC as desirable partners for research collaborations. Furthermore, the credentials of OMICRON and JUMC as a centre for educational and training events, through the organization of workshops, seminars, conferences, etc., have been reinforced.

The most valuable resources to emerge from the 3-year OMICRON Project are the new facilities and the new projects that they have attracted, which offer strong potentials for expansion, innovation and a pathway towards excellence, together with the human resources of young, enthusiastic, committed scientists who will take up the torch lit by OMICRON and carry it on to bigger and better things for JUMC, Krakow, and most importantly, for themselves.
Project Context and Objectives:
The strategy to enhance research potential at the Faculty of Medicine, Jagiellonian University Medical College (Krakow, Poland) in the OMICRON Project focuses on enabling high-throughput technologies as the key element, the lack of which is slowing down its scientific development at the moment.

The OMICRON Project proposes to achieve this goal through six Workpackages.
• WP1. Acquisition of state-of-the-art research equipment that makes high - throughput OMICS experiments in Krakow technically possible.
• WP2. Brain gain – recruitment of experienced researchers intended to attract scientists from other research centres with excellent skills and large experience in the areas associated with the OMICS centre.
• WP3. Transfer of knowledge and experience aims to obtain training not only from vendors of purchased instruments but also through intensive education at European partnering organisations to provide researchers with hands-on experience. A few leading scientific areas represented at JUMC were selected for this project. Training of local scientists in handling a large number of samples, performing high-throughput experimentation and analysing large amounts of data. Eminent researchers from partnering academic and industrial institutions across Europe coming for visits to provide advice on centre organisation and experimental issues. The workshops and research conferences on the technological and experimental aspects of next generation high-throughput technology were organized in Krakow. It helped to establish collaborations between researchers from Krakow and leading European scientific institutions.
• WP4. Increasing Faculty of Medicine visibility through dissemination and promotion actions. Dissemination of knowledge acquired during the project, in Poland and neighbouring countries, to initiate new generation molecular research in this region of Europe.
• WP5. Management. Management of the Project according to strict legal and financial rules applicable.
• WP6. External expert evaluation that provides an opportunity for external experts to evaluate the progress and management of the project.

The overall objective of the project was to up-grade, stimulate, unlock, develop and extend the research potential of the Faculty of Medicine. The specific objectives were:
- to up-grade and extend the laboratory equipment and research performance at the JUMC Faculty of Medicine allowing for the most advanced genomic and proteomic research;
- to attract, develop and retain the best research professionals of Polish origin and foreigners at the JUMC Faculty of Medicine;
- to develop the research skills of future leaders in the thematic domains concerned;
- to establish and expand networks across Europe to support high quality research, exchange of know-how and experience and ensure technology and knowledge transfer so that leading edge research can thrive at the JUMC Faculty of Medicine;
- to increase the visibility of excellence of the JUMC Faculty of Medicine and ensure the setting-up of long-lasting strategic partnerships with leading centres in the respective priority fields;
- to increase the participation of beneficiaries in scientific fields covered by HORIZON 2020.

In order to ensure a clear division of responsibilities, the following management and decision making structures and positions were in place:
• the Project Coordinator,
• Prof. Maciej Małecki, MD, PhD
• WP Leaders,
• the Project Administrator,

Steering Committee,
• prof. Piotr Laidler, PhD
• prof. Tomasz Grodzicki, MD, PhD
• prof. Tomasz Brzozowski, MD, PhD
• prof. Ryszard Korbut, MD, PhD
• Paweł Wołkow, PhD
• prof. Marcin Majka, PhD
• prof. Tomasz Guzik, MD, PhD
• assoc. prof. Marcin Barczyński, MD, PhD
• Marcin Jędrychowski, MSc
• Ewa Klepacz-Zielińska, MSc

International Advisory Board:
• Head of IAD: Prof. Keith Channon MD, FRCP, FMedSciProfessor of Cardiovascular Medicine Department of Cardiovascular Medicine NIHR Biomedical Research Centre, Oxford
• Prof. Sir John Burn (Newcastle University)
• Petr Dvorak, PhD (Masaryk University)
• Prof. Kari Stefansson (deCODE genetics)
• Prof. Patrick F. Chinnery (Newcastle University)
• Prof. Peter Schwarz, MD, PhD (University of Dresden)
• Prof. Anders Bergenfelz (Skåne University Hospital-Lund)
• Henning Morawietz, PhD, FAHA (University of Technology Dresden)
• Prof. Johann Bauersachs, MD, PhD (Medizinische Hochschule Hannover)
• Prof Mark McCarthy M.D PhD (Oxford Centre for Diabetes, Endocrinology & Metabolism)
• Prof. Mariusz Z. Ratajczak, MD, PhD (University of Louisville's James Graham Brown Cancer Center)
• Assoc. Prof. Charalampos G. Spilianakis, MD, PhD (Institute of Molecular Biology and Biotechnology, Greece)

Stakeholder Advisory Board
• Professor.Wojciech Nowak, MD, PhD - Rector of the Jagiellonian University
• Professor.Jacek Majchrowski - Mayor of the City of Krakow
• Marek Sowa - Marshal of the Malopolska Region
• Professor.Maciej Żylicz, PhD - President and Executive Director, Foundation for Polish Science.

Even though this project did not required the partnering organizations to create a European consortium, in the OMICRON project the international cooperation between JUMC Faculty of Medicine and nine partnering organizations was tied up.

The following European institutions agreed to collaborate with the Faculty of Medicine in the framework of the OMICRON Project:
1. University of Oxford, UK (Biomedical Research Centre, Department of Metabolic Diseases, Department of Cardiovascular Medicine)
2. King's College, University of London, UK
3. University of Wuerzburg, Department of Cardiology, Germany
4. Norwegian University of Science and Technology (NTNU), Trondheim, Norway
5. Department of Biology, Faculty of Medicine, Masaryk University, Brno, the Czech Republic
6. deCODE, Reykijavik, Iceland
7. Institute of Human Genetics, International Centre for Life Newcastle, UK.
8. Technical University in Dresden, Medical Clinic III, Genetics and Prevention of Diabetes, Germany
9. Institute of Molecular Biology and Biotechnology, Heraklion, Greece
10. Hannover Medical School, Germany
11. University of Glasgow, College of Medical, Veterinary and Life Science (MVLS)

Representatives of all above-mentioned organs were invited to meeting, conference and were asked about advises and support to the OMICRON project. They are to assess the progress made within the project implementation, as well as to monitor its impact and objectives achieved.

Project Results:
OMICRON project was the Coordination and Support Action within REGPOT initiatives, therefore there are not scientific and technological results, from more than 40 projects which were conducted within and thanks to OMICRON Laboratory. One beneficial effect of intense collaborative scientific activity has been the stimulation of postdoctoral researchers employed at the OMICRON unit to write their own grant proposals for scientific projects that would be conducted on the equipment located in the Centre for Medical Genomics – OMICRON.

The SWOT analyses prepared for the project application show that despite the strong research potential of the Jagiellonian University Medical College, mainly due to highly trained scientific staff, the main weakness was the lack of our own base/ infrastructure so a lot of experiments based on material and data collected in Poland were conducted in foreign laboratories. Creation of the modern laboratory highly increased the chance of fully enabling the scientific and academic potential of the JUMC staff.
A modern laboratory was opened in the building at Kopernika 7 Street. An important step in the creation of the laboratory was a grant accorded by the Polish Ministry of Science and Higher Education from infrastructure funds for science, which covered renovation of old premises. The Laboratory was officially opened in March 2013 although it took another few months for it to reach full functionality.

Description of facilities of the Center for Medical Genomics OMICRON:
As mentioned above, the Center is located at the Kopernika 7c building, shared with the Department of Medical Biochemistry. The Center is located on two floors, the ground floor (circa 162 m2) is the proper laboratory space; the underground floor (circa 310 m2) is for biobanking, computer servers, social room, lavatories, laboratory meetings, and a space for quiet work.

The underground floor includes:
1) Room for biorepository (biobanking), circa 53 m2;
2) Computer server room, circa 24 m2;
3) Social room with lavatories, circa 58 m2;
4) Conference room, circa 32 m2;
5) Office space, circa 26 m2;
6) Room for proteomics team (4 people), circa 21 m2;
7) Laboratory technicians’ room (4 people), circa 28 m2;
8) Postdoctoral fellows room (6 people), circa 25 m2;
9) Director’s room, circa 20 m2;
In addition underground floor contains communication corridors.

Ground floor is divided into three modules:
1) Pre-analytical module contains three rooms: nucleic acid isolation circa 17 m2, cell culture circa 12 m2, PCR setup and sequencing library preparation circa 21 m2, corridor circa 12 m2; altogether circa 62 m2;
2) Proteomics module contains one room with corridor, circa 31 m2;
3) Sequencing module contains one room with corridor, circa 69 m2;
The laboratory space on the ground floor is about 162 m2.

In the first phase equipment for genetic, genomic and proteomic tests, biomarking equipment and computer servers were purchased. The last purchase of smaller equipment was completed in the year 2015. The REGPOT funding was used to acquire new equipment for a total of €1.5 million, most notably, a Mass Spectrometer and HPLC, MiSeq and Microarray analysers, and a Biorobot .

Specification of OMICRON Laboratory Equipment:
1. Mass spectrometer
2. Equipment for nucleic acid electrophoresis and 2-dimensional protein electrophoresis with
imaging capabilities
3. Real-time thermocyclers (384 wells and 48 wells) and gradient thermocycler (96 well)
4. Microarray scanner (HiScan) with auxillary equipment and a next generation sequencer (MiSeq)
5. Ultra-low temperature freezer, liquid nitrogen storage tank, liquid nitrogen transport tank, cell
culture incubator
6. Ultrapure water maker
7. Centrifuges and a vacuum concentrator
8. Nucleic acid ultrasonic fragmenter
9. High-performance liquid chromatographer
10. Automated workstations for pre-PCR tasks and for post PCR tasks, nucleic acid quality and quantity
11. Automated biorobot for nucleic acid isolation
12. 12 laptop computers
13. Next generation sequencer (GS Junior)
14. Instrument for separation of DNA fragments of desired length
15. Small and medium laboratory equipment (e.g. pipets, scales, pH-meter etc.) in 9 parts
16. Craddle shaker (2 pieces)
17. Western blot instrument
18. 96-well head for the real-time PCR thermocycler
19. Microcentrifuges and minicentrifuges
20. UV/VIS spectrophotometer
21. Small cell culture incubator
22. Absorbance filters 490 and 660 nm
23. High-throughput tissue homogenizer
24. Additional rotators for the centrifuges
25. High-speed centrifuge
26. Pipets
27. Soft tissue homogenizer
28. Stereotactic table
29. 96-well plate shaker
30. Fluorescence microscope
31. Orbital shaker

The purchase of modern research equipment and the establishment of the OMICRON Laboratory with the goals to improve the quality of research in genetics, genomics, transciptomics and proteomics at the Medical Faculty of the Jagiellonian University Medical College has incredible impact on rasing the profil of unit internationally and has created opportunities to perform research by talented Polish scientists.
An important step in the Project was the employment of members of the research team and technicians to work in the Omicron laboratory. In accordance with appropriate procedures the competitions for each post were announced; several candidates applied for each post. Out of the applicants, the persons chosen were the most competent and best qualified for working in the planned laboratory. It is worth underlining that among them were people returning to Poland after several years at foreign academic centers. The Omicron project gave them a real chance to return to their country.
During the Project, Omicron laboratory employed ten postdoctoral researchers, who worked both on the Projects specific for the Departments, which prepared the Omicron grant application as well as on the projects assigned to the Omicron laboratory from outside collaborators. These collaborators included researchers from other Departments of the Medical College, Departments and Faculties of the Jagiellonian University, not associated with the Medical College and also from other Universities. During the project, seven laboratory technicians were employed. They had a chance to learn various technologies, associated with high-throughput genomic methods. At this point laboratory is involved in 42 projects, which are executed, at least partially at the Omicron laboratory. The duration of these projects extends above the duration of the project.
At the end of the project in May, 2015, the contracts of the employees were renewed for two additional years by the University in recognition of the success of the OMICRON Project and the strong accumulated know-how and expertise of the staff.

After the closing of the final phase of the project on May 15, 2015 the Omicron laboratory continues its activities. The Centre for Medical Genomics OMICRON is an independent unit of the Medical Faculty of the Jagiellonian University Medical College in Krakow, under the direct supervision of the Dean of the Medical Faculty. According to the statute of the Centre, the resources for functioning of the Centre are provided by the statutory funds of the Jagiellonian University Medical College by the decision of the Dean. Current support for the Centre, provided by the Dean of the Medical Faculty, is 450,000 PLN, covering expenses since the completion of the Omicron Project on May 15th until the end of Year 2015. This includes 305,000 PLN in the form of the salaries of the staff of the Centre and 145,000 PLN for the material expenses. All projects executed in the Omicron Centre have to provide financial resources for their relevant expenses (e.g. reagents, consumables, indirect costs).
The majority of the postdoctoral researchers and laboratory technicians, hired for the project are now employed at the laboratory.

Many laboratory techniques, mastered during the project were not available to the researchers from the Jagiellonian University at the inception of our project. Now, we continue to develop both wet lab and analytical methods, which were initiated during the project. This would not be possible, or at least our learning curve would be much steeper if not the training received during the Project and retained at the University by continued employment of our staff.

Potential Impact:
The outputs of the present project were expected to have a direct impact on the development of the scientific research capacity and capability of the Faculty of Medicine, Jagiellonian University Medical College.
The OMICRON work package design also had a profound impact at several levels including local positive influence on JUMC scientific community, regional impact in the southern Poland area, as well as impact at the level of the European Research Area.
The new generation of scientists trained at JUMC Faculty of Medicine will continuously boost the establishment of biotech companies and high-tech enterprises in the region. Creation of such competitive and advanced centre with international collaborations is likely to generate potential for future spin-off and spin-out companies and developments on the border of science and R&D.
The training opportunities in the foreign laboratories have been advertised within JUMC and a possibility for such training has been provided through a competitive application process. Conferences and meetings have all been opened to all scientists and provided strong boosts for the departments, which at present, do not use their resources to the full extent.

As the organizer of conferences, workshops, seminars and the visiting professorship programme proposed by OMICRON, JUMC Faculty of Medicin dramatically improved its recognition and visibility on the European arena and increased its European audience. The rise of visibility of the Faculty of Medicine was critical internationally for all scientists at JUMC.

Forecast of growth in users of OMICRON up to year 2020
1. We expect that until the year 2020, and beyond that date, Center for Medical Genomics OMICRON will have remained an independent unit within the structure of the Jagiellonian University Medical College.
2. We intend to keep the number of employees at least at the current level of 9 people (4 researchers-fellows with a PhD title, 4 researchers-technicians with MSc title, director of the center) or higher. We expect to increase employment in the Center to have in the near future one additional researcher-technician for the wet lab activities and another one for bioinformatics support.
3. We intend to update the equipment in the laboratory to keep up with the fast pace of progress in this area. In particular, we would like to acquire a mass spectrometer with higher sensitivity and a next generation sequencer with higher throughput.
4. During the project, OMICRON staff was involved in 42 projects. Only few of them have been completed so far. Some of these projects have been approved and are in the phase of data collection, however majority of them are in the execution phase now. We believe that the number of the projects, manageable for the staff of the Center, should be in the range of 30-40 projects, executed in parallel. Our efforts will be directed to work with our collaborators to expand small, pilot projects, which we are involved in now. We would like to help these small projects to grow into ones that make full advantage of high-throughput technologies available at OMICRON.

Therefore, our major goal in terms of the number of the projects, executed in our Center is not to constantly increase their number because this may eventually result in long queues until execution of the experiments. We would like to keep their number at a relatively constant level of 30-40 projects but to replace the completed projects with new incoming ones. Given the current interest of the scientific community at the Medical College in collaboration with the Center this should be possible to achieve.
However, we also want to saturate the projects with high throughput technologies. To achieve this goal we advise our collaborators which technologies available at OMICRON would add value to their projects. We help them from the stage of the study design through sample collection and wet lab experiments until data analysis, probably the most difficult phase for the clinicians. One of the basic measures of the success of programs that are aimed at increasing the scientific potential of an academic center is durability. In this context, it is worth underlining that after the closing of the final phase of the project on May 15, 2015 the Omicron laboratory continues its activities. The Medical Faculty assigned a yearly grant of 400 000 PLN from its statutory funds for the employment of the research teams and purchase of basic materials. The majority of the researchers hired for the project are now employed at the laboratory. Currently the laboratory is carrying out over 40 research projects of different size financed by national and European funds. In 2014 the Faculty Board decided to grant the Omicron center the status of an independent unit within the structure of the Faculty. All this constitutes a solid prognosis of the durability of the project.

The fact that today tens of research projects are being run or are being carried out, financed by national and European institutions, is best evidence of the importance of this infrastructure investment. The opening of the laboratory would not be possible without the participation of young researchers employed and trained thanks to Omicron funds. One cannot forget about the role of the international exchange organized as part of the project. The visits of over 36 professors from leading European, American, Canadian and Australian centers contributed to the improvement of the competences of researchers from the Jagiellonian University and other academic centers in Krakow. They also constituted excellent promotion of the university, city and country among internationally renowned research authorities. The participation of about 150 JU researchers in trainings, workshops and international scientific conferences is an investment in the future of the university.

The promotion of the project was visible in local and academic media, as well as in electronic media. A very important part in the implementing of WP 4 was contact with the media at a local, national and international level. The aim of this task was to maintain both general public and expert readership updated about the progress of the project. Information about the OMICRON Project was disseminated through the press, the Internet, radio and television.

In the new European Union perspective Horizon 2020, Krakow academic centers will attract further projects increasing their research potential.

An important part of social impact had the creation of the Stakeholder Advisory Board, which was established to serve as a consultative body. Members serving on the SAB included:
• Professor Wojciech Nowak, MD, PhD - Rector of the Jagiellonian University
• Professor Jacek Majchrowski - Mayor of the City of Krakow
• Marek Sowa - Marshal of the Malopolska Region
• Professor Maciej Żylicz, PhD - President and Executive Director, Foundation for Polish Science.

Stakeholders Advisory Board Members (or their representatives) took part in:
• the kick-off meeting that was organized in January 2012,
• the grand opening of the OMICRON Laboratory in March 2013,
• the OMICRON mid-term meeting that was organized in October 2013,
• the Recent Advances in Omics Research and the Dissemination Conference of the OMICRON Project in October 2014,
• the OMICRON Conference, EASD Study Group on Genetics of Diabetes meeting in May 2015.
The inclusion on the Stakeholder Advisory Board of the Marshal of the Malopolska region has opened the way for integration of OMICRON into the region and for having an input into regional issues, such as the formulation of a Smart Specialization Strategy. In addition, the involvement of regional government actors in the Project was important in promoting and highlighting the activities of the OMICRON Centre in a wider sphere. With respect to the national level, OMICRON received funding for the refurbishment of the laboratories via the Ministry of Science.

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