Applied Functional Genomics
20-23 August, 2004
University of Aarhus, Denmark

Organiser:

Brian Clark, University of Aarhus, Denmark

Report

Summary

After the sequencing of the human genome, functional genomics is increasingly important for the success of companies' genomics-based drug discovery and development efforts. It is not enough to know sequence information in order to utilize genomics to develop breakthrough drugs and diagnostics. One must also understand how genes and their products work, how they interact in pathways within the cell and the organism, and what roles they play in health and disease.

As a result, drug discovery researchers are in a "post-genomic", functional genomics era. Functional genomics aims to discover the biological function of particular genes, and how sets of genes and their products work together in health and disease. In its broadest definition, functional genomics encompasses many traditional molecular genetic and other biological approaches. In addition, functional genomics has come to be used to describe high-throughput approaches to whole-genome or system-wide molecular genetic studies. Many leading pharmaceutical companies are making or have made major investments in this field, often partnering with small genomics and biotechnology companies that are developing functional genomics platform technologies.

A possible definition is the development and application of global (genome-wide or system-wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics. Thus functional genomics is characterized by high throughput or large-scale experimental methodologies combined with statistical and computational analysis of the results. The fundamental strategy in a functional genomics approach is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion. Computational biology will perform a critical and expanding role n this area. Whereas structural genomics has been characterised by data management, functional genomics will be characterised by mining the data sets for particularly valuable information. Functional genomics promises to narrow rapidly the gap between sequence and function and to yield new insights into the behaviour of biological systems.

In this respect the central belief embedded in functional genomics is that the complete sequence of the genomes of many organisms, including humans, will change the way we do biology towards a more holistic view of biological systems which is significantly different from the classical idea of investigating "one (or a few) genes at a time".

Scientific content of and discussion at the event

The workshop consisted of five sessions and two supplementary plenary lectures for the discussion of specific major elements of functional genomics.

In the first session "High Throughput Technologies" examples were given by leading researchers in the field. A critical discussion took place to evaluate the state of the art in the application of high throughput microarrays etc. to make the participants to realise the advantages, drawbacks, and possible improvements in such technologies.

The second session for which we particularly asked the cooperation of the ESF Programme on "Integrated Approaches for Functional Genomics" concerned Bioinformatics, an essential underlying research activity for giving credence to characterising and determining the possible useful applications of the platform technologies used in the field. This session was supported and organised by the ESF contribution in addition to general ESF funding support.

The third session on protein profiling or commonly called "Proteomics" can be considered as the main theme of the workshop since both plenary lecturers overlapped with the session giving evidence of expertise in applying results to medical problems. Here we used the definition decided at a US National Research Council Hearing where the organiser participated. Thus the most useful definition of proteomics is likely to be the broadest: proteomics represents the effort to establish the identities, quantities, structures and biochemical and cellular functions of all proteins in an organism, organ, or organelle, and how these properties vary in space, time and physiological state. Proteomics is thus a huge, long-term task, much more complex than sequencing the genome.

The fourth session attempted to discuss briefly the current hot topic of "Epigenetics" since the importance to developing organisms of epigenetic events are more and more being realised to be involved in development and disease. Included in this session was not just damage to DNA and proteins in gene regulation but also knock down of genes.

Ageing research is now entering the post-genomic era. During recent years, a long list of genes has emerged that associate with various models of ageing in humans. The task now is firstly to evaluate the importance of these genes, mainly isolated from in vitro models, with respect to normal ageing and secondly to understand the functions of these genes and how they affect the process of ageing. Furthermore, we now accept the idea of the plasticity of lifespan. In this new concept, the emerging topic of epigenetics contributes of the order of 75% to the aging process. The fifth session discussed the scientific progress and future possibilities in this important topic.

In addition to the Plenary Lectures sponsored by the EFB and Novo Nordisk, there were special lectures sponsored by EFBIC (European Focus on Biotechnology in China) and Senetek PLC.
The final Scientific Programme is added to show the lecture topics (see point 4) and the course brochure including the abstracts.

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

Despite the fact that protein array technology has been around for more than a decade, the field is seeing an explosive progress and interest at the moment and is one of the most active areas emerging in biotechnology today. Protein arrays are solid-phase ligand binding assay systems using immobilised proteins in a highly parallel and miniaturised format. Their advantages include speed, automation, high sensitivity, economical use of reagents, and providing a large amount of data for single experiments. In 'capture arrays', ligand-binding reagents, usually antibodies, are used to detect target molecules in mixtures such as plasma or tissue extracts. For diagnostics applications, antibody arrays are used as analytical tools to perform multiple immunoassays in parallel, while in proteomics, they can quantitate and compare the levels of proteins in different samples in health and disease (protein expression profiling). Other 'functional protein arrays' are used to screen protein-protein, protein-DNA or protein-drug interactions.

However, there are several important technical challenges and bottlenecks in protein array technologies which need to be solved in order to achieve the maximum capability. Sensitivity, specificity and signal-to-noise in the multiplex format are major issues and will become more critical as the complexity of arrays is increased. In future we need to expand the knowledge base significantly from what we heard in this meeting.

As Steve Burrill of Burrill Associates in San Francisco recently expanded "We are just at the beginning of trying to understand functional genomics. It will be with us for the next 50-100 years". Thus all events such as our workshop at present is a preliminary step in defining the problem and testing new platform technologies. The complexity becomes evident by the recent determination (Oct. 2004) that the human genome contains only of the order of 25,000 genes whereas there are probably well over 100,000 gene products to be defined and explored.

The EFB Section of Applied Functional Genomics was very satisfied with and gratified by the cooperation with the ESF cooperation via the programme on Integrated Approaches for Functional Genomics. We look forward to future collaboration and cooperation possibly with common membership. Also stimulation of research cooperations will create a favourable European atmosphere for growth of much needed new technology and its commercialisation in Europe.

Final programme for the meeting

Workshop on Applied Functional Genomics

Friday 20 August
17:00-18:00 Registration

18:00-18:10 Welcome by Brian Clark

18:10-19:00 EFB Plenary speaker
Julio Celis, The Danish Cancer Society, Copenhagen, Denmark:
Integrating proteomics and functional genomics in translational breast cancer research

19:00-20:30 Welcome buffet reception
in the Lecture Theatre Building

Saturday 21 August
08:30-09:00 Registration

High Throughput Technologies

09:00-09:35 Jørn Koch, Aarhus University Hospital, Denmark:
Allele discriminating single molecule, single cell, detection in high throughput formats

09:35-10:10 Ulf Landegren, Rudbeck Laboratory, Uppsala, Sweden:
Tools to study biomolecules, singly and in parallel

10:10-10:45 Coffee break

10:45-11:20 Olli Kallioniemi, VTT Technical Research Centre of Finland, Turku:
Biochip technologies for functional and translational genomics

11:20-11:55 Jörg Hoheisel, Deutsches Krebsforschungszentrum, Heidelberg, Germany:
Microarrays as a means for functional analyses

11:55-12:30 Lars-Eric Utterman (GE Healthcare),:
The latest development within GE Healthcare with emphasis on proteomics

12:30-14:00 Lunch in the Math Institute Canteen

The ESF Bioinformatics Symposium

14:00-14:35 Søren Brunak, Technical University of Denmark, Copenhagen:
Predicting dynamic changes in protein features during the cell cycle

14:35-15:10 Palle Villesen, Bioinformatics Research Center, University of Aarhus, Denmark:
A new database of human endogenous retroviral sequences reveals hundreds of long viral open reading frames

15:10-15:45 Alfonso Valencia, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain:
A Computational Systems Biology approach to the study of protein interaction networks

15:45-16:20 Coffee break

16:20-16:55 Rolf Apweiler, EMBL Outstation, EBI, Hinxton, UK:
Standardisation and integration of proteomics and genomics data

16:55-17:30 EFBIC Lecturer
Wang Jun, Beijing Genomics Institute (BGI), WIGS, China:
Vertebrate gene predictions and the problem of large genes

17:30-18:00 Poster session

Sunday 22 August
Protein Profiling/Proteomics

09:00-09:35 Mike Taussig, The Babraham Institute, Cambridge, UK:
Protein Arrays: New tools for proteomics and biotechnology

09:35-10:10 Peter Roepstorff, University of Southern Denmark, Odense:
Determination of post translational modifications in proteomics

10:10-10:45 Coffee break

10:45-11:20 Anne-Claude Gavin, Cellzome AG, Heidelberg, Germany:
A proteomic approach for the charting of cellular pathways

11:20-11:55 EFBIC Lecturer
Zeng Rong, Shanghai Institutes for Biological Sciences, CAS, China:
Systematic and comparative analysis of hepatocellular carcinoma from cells to clinical tissues

11:55-12:30 Angus King, ACE BioSciences A/S, Odense, Denmark:
Discovery and validation of novel vaccine candidates for infectious diseases

12:30-14:00 Lunch in the Math Institute Canteen

Epigenetics, Genetic Engineering and the RNAworld

14:00-14:35 Lise Lotte Hansen, University of Aarhus, Denmark:
Epigenetics. From 5-methylcytosine to BORIS

14:35-15:10 Wolf Reik, The Babraham Institute, Cambridge, UK:
Imprinting and epigenetic reprogramming in development and disease

15:10-15:45 Lars Bolund, University of Aarhus, Denmark:
Transgene expression and genome editing for functional genomics research, biotech production and gene therapy

15:45-16:20 Coffee break
16:20-16:55 Juri Rappsilber, Institute for Molecular Oncology Foundation (IFOM), Milan, Italy: The protein component of epigenetics

16:55-17:30 Bertrand Friguet, Universite Denis Diderot, Paris, France:
Oxidatively modified proteins and aging

19:00 Conference dinner in "The Old Town"

Monday 23 August
09:00-10:00 NOVO NORDISK A/S Plenary speaker
Mathias Uhlen, Royal Institute of Technology (KTH), Stockholm, Sweden:
Antibody-based tissue proteomics to study the human proteome

Ageing and Age-related Diseases

10:00-10:40 EFBIC Lecturer
Yang Huanming, Beijing Genomics Institute (BGI), WIGS, China:
From genomics to health

10:40-11:10 Coffee break

11:10-11:50 SENETEK PLC Lecturer
Claudio Franceschi, Interdepartmental Centre "L. Galvani" for integrated studies on Biophysics, Bioinformatics and Biocomplexity, University of Bologna, Italy: The genetics of human longevity helps in disentangling the molecular basis of major age-related diseases

11:50-12:30 Olivier Toussaint, University of Namur (FUNDP), Belgium:
Stress-induced premature senescence and some of the 'omics


List of participants

Jan Alsner, Dept. Experimental Clinical Oncology, Nørrebrogade 44, Bygn. 5, 8000 Århus C, Denmark
Birte Andkjæ,r University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Rolf Apweile,r EMBL-EBI Wellcome Trust Genome Campus, CB10 1SD Cambridge, UK
Iordanis Arzimanoglou, Biomedico/Science Park Brendstrupgaardsvej 102, 8200 Århus N, Denmark
Lars Bolund, Inst. Of Human Genetics, Aarhus Universitet 8000 Aarhus C, Denmark
Søren Brunak, CBS, Biocentrum-DTU Building 208, Kemitorvet 2800 Kgs. Lyngby, Denmark
Julio Celis, Danish Cancer Society, Strandboulevarden 49 2100 København Ø, Denmark
Brian Clark, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Telma Crugliano, University Magnae Graecia of Cantanzaro, Campus of Germaneto 88100 Catanzaro, Italy
Yutao Du, Research Centre Foulum, PO Box 50 8830 Tjele, Denmark
Junxin Duan, Novozymes China, 14 Xinxi Lu, Shandi Zone, Haidian District, 100085 Beijing, China
Domenico Focá, University Magnae Graecia of Cantanzaro, Campus of Germaneto, 88100 Catanzaro, Italy
Claudio Franceschi, Dept. Experimental Pathology, Via S. Giacomo 12, 40126 Bologna, Italy
Bertrand Friguet, University Paris 7 - Denis Diderot EA 3106 - LBBCV, cc 7128, 2 Place Jussieu 75005 Paris, France
Anette Frost Jensen, Novo Nordisk R&D Novo Nordisk Park 2760 Måløv, Denmark
Cosimo Gasparri, University Magnae Graecia of Cantanzaro, Campus of Germaneto, 88100 Catanzaro, Italy
Anne-Claude Gavin, Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Regina Gonsale,z Dosal University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Birgitte Hafjall, Amersham Biosciences, Huginsvej 8, 3400 Hillerød, Denmark
Lise Lotte Hansen, University of Aarhus, Dept. of Human Genetics, The Bartholin Building, 8000 Århus C, Denmark
Lisbeth Heilesen, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 1,0 8000 Aarhus C, Denmark
Jörg Hoheisel, DKFZ Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Yang Huanming, Beiing Genomics Institute, B6 Airport Industrial Zone, 101300 Beijing, China
Sergiy Ivakhno, Taras Shevchenko Kyiv National University, Yakuba Kolosa 8v 24, 03148 Kyiv, Ukraine
Helle Jakobsen, University of Aarhus, Dept. of Molecular Biolog,y Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Wang Jun, Beijing Genomics Institute, Watson Institute, B-6 Airport Industrial Zone, Beijing 101300, China
Just Justese,n Dept. of Molecular Biology, CF Moellers Alle 130, 8000 Aarhus C, Denmark
Søren Kahns, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Olli Kallioniemi, VTT Miedical Biotechnology & University of Turku Itäinen Pitkäkatu 4A, 20520 Turku, Finland
Crispin Kirkman, Emerging Technologies Network Agency, William Russell House, The Square GU18 5SS Lightwater, England
Jørgen Kjems, Aarhus Universitet C. F. Møllers Allé, 8000 Aarhus C, Denmark
Heinrich Klefenz, RTM Resources + Technologies - Management, Hauptstrasse 35, 76879 Bornheim, Germany
Jørn Koch, Institute of Pathology Nørrebrogade 44 8000 Århus C, Denmark
Steen Kolvraa, Institutr of Human Genetic, University of Aarhus, 8000 Århus C, Denmark
David Kraft, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Peter Kristensen, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej, 10 8000 Aarhus C, Denmark
Marianne Kyndi, Århus Sygehus, Dept of Exp. Clinical Oncology, Nørrebrogade 44, Bygn. 5, 8000 Århus, Denmark
Ulf Landegren, Uppsala Universitet, Rudbecklab Plan 2, 85185 Uppsala, Sweden
Mildrid Langset, VWR International AS, PO Box 45, Kalbakken, 0901 Oslo, Norway
Iana Lesnikova Nielsen, Pathological Institute, Aarhus Kommunehospital Tilst Skolevej 26, 8381 Tilst, Denmark
Zheng Liu, Novozymes China 14 Xinxi Lu, Shangdi Zone, Haidian District, 100085 Shangha,i China
Jian Liu, Dept. of Human Genetics, Bartholin Bld., 8000 Århus C, Denmark
Jakob Lohmann, Inst. Of Pathology, Aarhus Sygehus Nørrebrogade 44, 8000 Aarhus C, Denmark
Laura Luberto, University Magnae Graecia of Cantanzaro, Campus of Germaneto, 88100 Catanzaro, Italy
Fransisco Mansilla, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Kjeld Marcker, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Århus C, Denmark
Tinne Nielsen, Department of Clinical Oncology, Nørrebrogade 44, 8000 Århus, Denmark
Ruth H. Paulsse, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway
Karen Pihl-Carey, BioWorld Today, 228 Lartry Drive 17356 Red Lion PA, USA
Juri Rappsilber, IFOM, Via Adamello 12, 20139 Milan, Italy
Wolf Reik, The Babraham Institute, Babraham Research Campus CB2 4AT Cambridge, England
Peter Roepstorff, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark
Zeng Rong, Shanghai Institutes for Biological Sciences, 320 YueYang Road, 200031 Shangha,i China
Olaug Rødningen, Genetics Department, The Norwegian Radium Hospital, Montebello 0310 Oslo, Norway
Elise Røge Nielsen, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Claudio Scafoglio, Dept General Pathology, 2nd University of Naples, vico De Crecchio7, 80138 Napoli, Italien
Ma ShiLiang, Dept. of Molecular Biology, C.F. Møllers Alle 130, 8000 Århus C, Denmark
Gunhild Siboska, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Brita Singers, Århus Sygehus, Dept of Exp. Clinical Oncology, Nørrebrogade 44, Bygn. 5, 8000 Århus, Denmark
Csaba Soti, Semmelweis University Puskin u. 9., H-1088 Budapest, Hungary
Magnus Stougaard, Inst. Of Pathology, Aarhus Sygehus, Nørrebrogade 44, 8000 Aarhus C, Denmark
Jens Sundbye, European Federation of Biotechnology, Branch Office, Science Park, 8200 Århus N, Denmark
Prashanth Suravajhala, Department of Life Science, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
Renuka Suravajhala, Department of Life Science, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
Ilona Sørensen, Danish Institute for food and Vet. Reserch, Mørkhøj Bygade 19, 2860 Søborg, Denmark
Mike Taussig, Babraham Institute Cambridge, CB2 4AT Cambridge, England
Olivier Toussaint, University of Namur URBC, Rue de Bruxelles, 61 5000 Namur, Belgium
Mathias Uhlén, KTH Biotechnology Royal Institute of Technology, SE-10691 Stockholm, Sweden
Lars Eric Utterman, GE Healthcare Björkgatan 30, 75184 Uppsala, Sweden
Alfonso Valencia, National Centre for Biotechnology Campus UAM. Cantoblanco, 28049 Madrid, Spain
Palle Villesen, BiRC - Bioinformatics Research Center Høegh-Guldbergs Gade 10, Building 090, 8000 Århus C, Denmark
Simon Wittrup Nielsen, University of Aarhus, Dept. of Molecular Biology, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark
Oscar Yanes, Institut de Boitecnologia i Biomedicina, Universitat Autónoma de Barcelona, 08192 Cerdanyola del Vallés, Spain
Magdalena Zajac, Inst. Of Pathology, Aarhus Sygehus Nørrebrogade 44 8000 Aarhus C, Denmark