Advances in Molecular Mechanisms of Disease - High Throughput platforms and Advances in Imaging
23-25 March 2009
Oslo, Norway

Organisers:

Draft Report

Summary

The main purpose of the meeting was to provide an overview of recent advances in Molecular Medicine, with a particular focus on modern imaging techniques and high throughput technologies. Our ultimate goal was to increase the awareness among the young scientists of the technologies that are currently available and to help them get access to these techniques.

To achieve this, we set up two-day in-depth courses on new high throughput sequencing technologies and imaging technologies running in parallel followed by a three-day broad scope symposium addressing both fields. During the courses, in total 22 lectures were given covering practical aspects as well as their applications to study on disease mechanism (see next section for details of scientific content). The courses were organised in relatively small group so young scientists had full opportunity to ask questions and discuss their own research challenges with the lecturers from different area of expertise. The content of the symposium further extended the scope to interdisciplinary subjects covering novel applications on studies of disease mechanism using emerging technologies. We also included presentations of available research resources including databases, statistical tools, bioinformatics tools and European research platforms such as EMBL-European Molecular Biology Laboratory Nordic nodes, ESFRI- European Research Infrastructure including BBMRI, EATRIS and Elixir (details of scientific content please see next section). The symposium encouraged discussion between the young researchers and the technology representatives potentially opening doors for future collaboration and new ideas. In total, 42 students signed up for the courses and nearly 60 persons registered to the symposium. 17 tutors gave lectures to the students during the courses while 23 speakers (four of them were course tutors as well) gave talks during the symposium.

We aimed at setting up a high profiled meeting at the beginning. Based on the scientific content of the programme and list of speakers, we believed that this first Nordic initiative has achieved this aim. For future considerations, more effort could be contributed to advertise and attract more young scientists to take part in the event in order to maximise its impact. Another approach could be that if funding is sufficient, we should consider subsidising students travel grant through a review application mechanism as meetings in the Nordic countries usually imply higher travel and accommodation costs compared to other European countries.

Scientific Content

The meeting was set up to consist of three interdisciplinary parts – the symposium, HT-
Sequencing course and a course in biological imaging having the two courses in parallel followed by the symposium. The content of the two courses focused on practical applications of the technologies aiming at providing students and young scientists most up-to-date knowledge that can be potentially utilised for their own research. As for the symposium, the content had broader perspectives. Students, young scientist as well as more established scientists could gain update on the most recent development of the field in terms of science and technology advancement and available infrastructure platform and network. Further description of the scientific content and discussion at the event was detailed in the following paragraphs.

Course: State-of –the-Art High Throughput Sequencing Technologies
The course in High Throughput (HT) Sequencing Technologies illuminated recent developments in the rapidly advancing technology. The presentations outlined the technology overviews of modern HT-sequencing platforms as well as their applications to biomedical study. "Update on Next-Generation Technologies" gave an extensive overview to update everyone on capabilities of the novel techniques. Followed by the “Specific Biological Applications” Session where Jussi Taipale, Anna Kiialainen and Kerstin Lindblad-Toh presented their research as examples using high throughput technology to solve biological questions. Due to the rapid advance in the development of High Throughput Sequencing solutions and the fact that many of the technologies are designed hand in hand with researchers and companies we included in the “Practical Considerations” session a presentation of the technology leading company, ILLUMINA’s new genome analyser system (Mark Ross). This new development enables small labs to quickly generate highly accurate results for genomics, epigenomics, analysis of gene expression and protein-nucleic acid interactions. During the final lecture session addressing data handling and analysis, students had the opportunity to acquire knowledge on powerful biostatistical analysis tools, bioinformatics architecture dealing with massive data production and storage as well as resources of existing databases (Steve Sherry, dbGaP). With a relatively small group of students at the course, students were able to discuss in depth with the lecturers regarding questions from different research aspects. It is our view that the participants have benefited from this course by increasing their competence on current technologies, their applications and limitations.

Course: Advances in Imaging Technologies
The program for the bioimaging course consisted of lectures by leading scientists with experience in the use of imaging tools for pre- and clinical research, with a special emphasis on neurodegenerative diseases. The lectures ranged from basic principles of multiphoton microscopy (by a pioneer in the field, Denk), and other imaging techniques, to their application in diseases like Parkinson’s (Brooks & Frackowiak), Alzheimer’s (Nordberg) and Huntington’s diseases (Sachill). Principles to be taken into account regarding animal experimentation were also presented (van der Linden). Most of the discussions during the course and the symposium focused on the advantages and disadvantages of the current technologies, as well as the limitations regarding analysis and interpretation.

In addition to the presentations the lecturers and participants who all participated throughout the course engaged in deep discussions on both biomedical focus points and possibilities within the novel approaches. Both courses were closed with a site visit to the University hospital in Oslo. The site visit gave the opportunity to the participants (included some of the lecturers) to come into contact with the core of clinical research in Oslo, currently one of the most advanced and flexible centers for clinical experimentation that includes bioimaging and HT sequencing facilities both for clinical and experimental research.

Symposium: Advances in Molecular Mechanisms of Disease
During the symposium, the presentations related to bioimaging focused on the experimentally (Choquet & Meisel) and clinically relevant applications (Brooks, Frackowiak & Nordberg). The study of molecular mechanisms related to neurotransmitter movement and immuno-responses upon stroke were some of the topics related to the use of live cell imaging technologies. On the other hand, the applicability of PET and MRI in vivo imaging was exemplified in the diagnosis and assessment of therapies for Alzheimer’s and Parkinson’s disease.

The symposium also included aspects such as equipment, reagents and experimentation in HT sequencing. These aspects usually represent major investments for research institutions; therefore, it was important to demonstrate different options available and their advantages and disadvantages. The symposium concentrated on giving an update on how to effectively exploit the capabilities in a given technology platform since nowadays it is crucial to make full benefit of the investment before the technology becomes more or less obsolete. One important aspect was that participants in addition to gaining knowledge on their own areas of expertise also learned from other sites that are currently using different approaches (i.e. K Lindblad-Toh, H Stunnenberg, J den Dunen). In addition, Samuli Ripatti outlined the power of large scale collaboration in EC FP7 supported project “ENGAGE” for the study of genome wide profiles of common diseases and Kerstin Lindblad-Toh described the large international network approach to study disease genes in dogs. In the Applications of Emerging Technologies session Andres Metspalu presented the new study on the genetic structure of the Europeans and Ann-Christine Syvänen presented the groups new findings on the epigenomics of leukemia. This was followed by a detailed overview on HT-sequencing in human genomics by Robert Lyle. The keynote lecture (G-J van Ommen) particularly outlined how innovative HT biomedical technology could play crucial role in dissecting complex diseases potentially leading to improvement or discovery of novel methods for disease diagnosis, treatment and prevention. The clinical/pharmaceutical potential generating from the studies of biobank resources was also addressed during the lecture.

Large-scale data handling and analysis is a real challenge for HT technology platforms. The symposium included presentations that covered comprehensive overview on available biostatistics analytical tools for genome-wide data (J Palmgren) as well as recent development of bioinformatics tools (J Thornton) and concepts of databases and data archiving for genotyping data (P Flicek). By gaining insight of these available resources, participants could relate to their own study design with the approach to achieve effective and accurate study output.

There were also presentations from the major European technology platform providers and developers for molecular medicine. These presentations addressed EMBL research networks in the Nordic countries by their leaders (FIMM: Finland, NCMM: Norway and MIMS: Sweden) introduced by the Director of EMBL (I Mattaj). The major ESFRI European research infrastructures – European Advanced Translational Research Infrastructure in Medicine (EATRIS), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI), and ELIXIR-Data for Life (presented by their leaders A Aperia, K Zatloukal, & J Thorton, respectively) were also presented at the symposium. The purpose of these presentations was to give an overview of the available resources at the European level. We were really pleased that the leaders of all these research networks and infrastructure providers were able to attend allowing these session not only to be informative to the audience but also served as valuable discussion opportunities for the EMBL-nodes as well as for the ESFRI approaches.

Assessment of the results & impact of the event on the future direction of the field

This first Nordic collaborative initiative in Molecular Medicine contributed to give an overview of the ongoing research activities in the Nordic region, bringing awareness of the possibilities that are available in the neighbouring countries. It also gave the opportunity to Nordic PhD students and young researchers to meet some of the most leading scientists in the fields of bioimaging and HT-sequencing as well as the leaders of some of the most prestigious research networks and infrastructures in Europe. With a relatively smaller scale of the meeting, the participating young scientists had the opportunity to closely interact with the invited speakers. To maximise the impact of such event, in the future we should try to attract more young scientists from other countries to attend the meeting in Nordic countries by means of subsidising travel grant. In general meeting in Nordic countries often implies high costs in connection to travel and accommodation. This could be shown from the geographical distribution of the participants. Nearly 80% of the participants came from Nordic countries; among them, 80% were from the hosting country, Norway. In the future if funding is sufficient we may consider subsidising students travel grant through a review application mechanism. Improvement of pre-event organisation and advertisement is another approach to attract more young scientists to such event.

We believe that this kind of event, where a mixed scientific program is provided, is necessary to demonstrate the capacity and opportunity of the existing European research network and infrastructure platform to young researchers. Even though we noticed that young scientists often preferred a more research-oriented and subject- targeted program rather than a program combined with demonstration of research infrastructure and network, we still recognised the importance of bringing awareness to young researchers regarding opportunities to interact with already existing networks in Europe and to learn how to fully utilise the resources. For future events, we consider that it would be better to include this type of sessions as satellite events and encourage young scientists to take part and get involved at early stage.

Programme

Day 1 - Monday, June 8th
10.45 Welcome by the President of the University of Oslo, Professor Geir Ellingsrud

Course: State-of-the-art High Throughput Sequencing Technologies
Session 1: Update on the next-generation technologies
11.00 Kjetill S. Jakobsen (University of Oslo, Norway)
How new technology changed the concept of sequencing
11.40 Olle Ericsson (Uppsala University, Sweden)
Targeted capture technologies
13.00– 14.00 Lunch
Session 2: Specific Biological Applications
14.00 Anna Kiialainen (Uppsala University, Sweden)
Identification of regulatory genetic variation in childhood acute lymphoblastic leukemia
14.40 Jussi Taipale (University of Helsinki, Finland)
Analysis of DNA-binding proteins using multiplexed massively parallel sequencing
15.20 Kerstin Lindblad-Toh (Broad Institute, USA/Sweden)
Directed sequencing and de novo genome assembly

Course: Advances in imaging technologies
Session 1: Confocal microscopy
11.00 Timo Zimmermann (European Molecular Biology Laboratory, Germany)
Development and considerations
11.40 Timo Zimmermann (European Molecular Biology Laboratory, Germany)
Dye separation, multicolor imaging and analysis
12.20 Adriaan Houtsmuller (Josephine Nefkens Institute, The Netherlands)
FRAP, FRET and FLIP: basics and principles
13.00 – 14.00 Lunch
Session 2: Multi-photon laser scanning microscopy
14.00 Erlend Nagelhus (CMBN, University of Oslo)
Imaging of astrocytes
14.40 Winfried Denk (Max-Planck-Institute for Medical Research, Germany)
Live cell imaging
15.20 Winfried Denk (Max-Planck-Institute for Medical Research, Germany)
In tissue slices

Day 2 – Tuesday, June 9th
Course: State-of-the-art High Throughput Sequencing Technologies
Session 3: Practical considerations
10.00 Mark Ross (Illumina, UK)
Sequencing Human Genomes with the Genome Analyzer
11.00 Anna Kiialainen (Uppsala University, Sweden)
Applications of Emerging Technologies
11.45 – 12.00 Coffee break
Session 4: Data handling and analysis
12.00 Yudi Pawitan (Karolinska Institutet, Sweden)
New advances in biostatistics
13.00 – 14.00 Lunch
14.00 Guy Cochrane (European Bioinformatics Institute, UK)
Data storage and challenges of bioinformatics
15.00 Steve Sherry (National Center for Biotechnology Information, USA)
dbGaP: the NCBI database of genotypes and phenotypes
Course: Advances in imaging technologies
Session 3: Functional Brain imaging
09.00 David Brooks (Imperial College London, UK)
PET
10.00 Richard Frackowiak (UCL Institute of Cognitive Neuroscience,UK)
Plasticity and reorganisation of motor systems during recovery using classical
MRI techniques
11.00 – 11.15 Coffee break
Session 4: Practical considerations and applicability
11.15 Anthony Holtmaat (University of Geneva, Switzerland)
Imaging dendritic changes in the brain in vivo
12.00 Agneta Nordberg (Karolinska Institutet, Sweden)
PET in combination with in vitro autoradiography
13.00 – 14.00 Lunch
14.00 Annemie van der Linden (University Antwerpen, Belgum)
MicroMRI in research animals
15.00 Rachell Sachill (University College London, UK)
Bioimaging in Huntington’s Disease
For both courses:
16.30 Session 5: Site visit to University Hospital Oslo Rikshospitalet - The Interventional Centre
18.00 Welcome Reception for Symposium and ScanBalt meeting at Oslo City Hall

SYMPOSIUM
Day 3 - Wednesday, June 10th
09.00 Welcome by Åsa Elvik, Secretary of State, Ministry of Education and Research,
Arvid Hallén, Director General, The Research Council of Norway and
Finn Wisløff, Dean, Medical Faculty
Session 1: Genetics and Imaging
09.45 Agneta Nordberg (Karolinska Institutet, Sweden)
Imaging and association studies for early diagnosis of Alzheimer’s disease
10.25 Richard Frackowiak (UCL Institute of Cognitive Neuroscience,UK)
Structural MRI and genetics: a bridge from molecule to behaviour
11.00 – 11.10 Coffee break
Session 2: 1000 genomes and beyond
11.10 Samuli Ripatti (University of Helsinki, Finland)
Genome wide profiles of common diseases
11.40 Kerstin Lindblad-Toh (Broad Institute, USA/Sweden)
Finding disease-related genes in other species
12.10 – 13.00 Lunch
15.00 – 15.15 Coffee break
Session 3: Applications of Emerging Technologies
(run in parallel with ScanBalt Meeting)
15.15 David Brooks (Imperial College London, UK)
Brain functional reorganisation in disorders of motor control Using PET- Imaging
15.55 Robert Lyle (University Hospital Oslo)
The impact of high-throughput sequencing on human genetics
16.40 Daniel Choquet (Université Bordeaux 2, France)
Two-photon optical imaging - Single molecule tracking coupled to nanotechnology/
quantum dots
17.20 Ann-Christine Syvänen (Uppsala University, Sweden)
Allele-specific regulation of gene expression by DNA methylation in primary
leukemic cells
18.00 Andres Metspalu (University of Tartu, Estonia)
Genetic structure of Europeans - a view from the North-East

ScanBalt Academy Meeting Soria Moria Conference Hotel, Store Sal
Day 3 - Wednesday, June 10th
Chairman – Kaare Norum
13.00 Welcome by President of the ScanBalt Academy Kaare R. Norum, Oslo
13.15 Jonas Gahr Støre (Minister of Foreign Affairs, Norway)
The High North Policy: Implications for collaboration with Russia on Science
13.25 Peter Agre (Johns Hopkins School of Public Health, USA)
The role of Science in Diplomacy; Fridtjof Nansen as a role model for the 21st Century
14.00 Hans Metelmann (Schwerin, Chair of ScanBalt)
ScanBalt: a Biomedical region on the top of Europe
14.15 Liisa Hakamies-Blomqvist (NordForsk)
New Nordic Research initiatives
14.30 – 15.00 Coffee break
ScanBalt Academy Meeting continued (run in parallel with Symposium)
Chairman - Kaare Norum
15.00 Jeanette H. Andersen (University of Tromsø, Norway)
Marine Bioprospecting in the North
15.15 Fredrik Almqvist (University of Umeå, Sweden)
New antibiotics from the Artic Ocean
15.45 Nils Christian Stenseth (University of Oslo, Norway)
The Ecology of the Barents Sea
16.15 Viktor Berger (White Sea Biological Station, St. Petersburg)
White Sea: Ecology and Environment
16.45 Erik Bonsdorff (Åbo Akademi University, Finland)
The Ecological and Political Challenges of the Baltic Sea
17.15 End ScanBalt Meeting

SYMPOSIUM
Day 4 - Thursday, June 11th
08.30 Gert-Jan B. van Ommen (Leiden University Medical Center, The Netherlands)
Keynote Lecture: Genomics research guiding therapy and supporting biobanking.
Session 4: Omics and Imaging to study mechanisms underlying disease
09.10 Olli Kallioniemi (Institute for Molecular Medicine, Finland)
Cancer genetics and systems biology
09.50 – 10.00 Coffee break
10.00 Lennart Martens (European Bioinformatics Institute, UK)
Proteomic studies in human diseases
10.40 Andreas Meisel (Charité Universitaetsmedizin Berlin, Germany)
Novel strategies of immune suppression in stroke
Session 5: Databases and bioinformatics
11.20 Juni Palmgren (Karolinska Institutet, Sweden)
New advances in biostatistical analyses of genome wide data
12.00 – 13.00 Lunch
13.00 Janet Thornton (European Bioinformatics Institute, UK)
New tools of bioinformatics
13.40 Paul Flicek (European Bioinformatics Institute, UK)
Genotyping databases and data archiving
14. 10 – 14.30 Coffee break
Session 6: Presentation of European platforms: European Molecular Biology Laboratory and Nordic Nodes for Molecular Medicine
14.30 Iain Mattaj (Director General of EMBL)
European Molecular Biology Laboratory (EMBL)headquarters
15.10 Olli Kallioniemi (University of Helsinki, Finland)
Institute for Molecular Medicine Finland (FIMM)
15.50 Kjetil Taskén (University of Oslo, Norway)
Centre for Molecular Medicine Norway (NCMM)
16.30 Bernt Eric Uhlin (Umeå University, Sweden)
Laboratory for Molecular Infection Medicine Sweden (MIMS)
17.10 Anita Aperia (Karolinska Institutet, Sweden)
European Advanced Translational Research Infrastructure in Medicine (EATRIS)
Session 7: Poster session
18.00 – 19.00 Poster presentations
20.00 Dinner at Soria Moria

SYMPOSIUM
Day 5 - Friday, June 12th
Session 8: European platforms – part 2: ESFRI European Research Infrastructure
09.00 Kurt Zatloukal (Medical University of Graz, Austria)
Biobanking and Biomolecular Resources Research Infrastructure (BBMRI)
09.40 Janet Thornton (European Bioinformatics Institute, UK)
ELIXIR – Data for Life
Session 9: Tools for the study of epigenetic control of genome function
11.10 Henk Stunnenberg (Radboud University of Nijmegen, The Netherlands)
Deciphering cancer epigenetics
11.50 Johan den Dunnen (Leiden University Medical Center, The Netherlands)
Sequencing and transcriptomics
12.30 LUNCH – End of Symposium