The discipline of systems biology integrates physics, mathematics and engineering with biology. At its heart are mathematical models that attempt to integrate all relevant data to come up with approximations of “how biology works”.
Recommendations for systems biology
1. A European road map. A task force should be established in which the major stakeholders are represented, comprising top scientists, industry, European science organisations and funding agencies, and representatives of the European Commission.
2. European Reference Laboratories. Cost-effective coordination of a European systems biology programme requires a consortium of European Reference Laboratories that combine all relevant scientific disciplines and the know-how to provide outstanding expertise for core aspects of systems biology.
3. Cooperation between industry, academia and funding agencies. The Europe-wide approach will require an integrative and larger-scale level of funding than provided by grant systems now. A new financial model should be developed on the basis of cooperation between academics, industry or EC-related organisations.
4. Public acceptance. Large-scale European efforts will be viable only if the general public accepts and endorses the underlying ideas and goals of the Grand Challenge for European Systems Biology programmes.
5. Training and education. In contrast to the present practice of educating scientists in the classical disciplines, the systems biology approach requires new thinking across classic scientific borders. Currently, progress in biology is hampered by the largely single-discipline teaching systems in Europe.
Language threat to big science
The shift to big science – involving the joint effort of a number of disciplines and of more and more expensive equipment – is inevitably threatened by language barriers (both across disciplines and from one nationality to another), a shortage of equipment, and the absence of funding mechanisms to support such cross disciplinary and large-scale research.
There is a need to develop new approaches to focus, synergise, manage and fund large national and international programmes to explore the possibilities offered by systems biology, says the European Science Foundation (ESF) in its latest Forward Look report, “Systems Biology: a grand challenge for Europe; an attempt to identify how research in Systems Biology could be accelerated and developed further in Europe”, published earlier this week.
John Marks, Chief Executive of the ESF, said the report highlights Europe’s potential to be at the forefront of pinpointing the system causes of diseases.
But to achieve this, “It is necessary to develop a well coordinated effort, bringing together the many different research activities in Europe, and complement this with joint development of basic technologies, reference labs and training a new generation of researchers,” he said.
Twelve visions
The report includes 12 essays from leading experts in academia and industry, who give their vision of what systems biology could deliver.
Until recently, researchers tended to focus on identifying individual genes and proteins and pinpointing their role in the cell or the human body. But molecules almost never act alone, according to Lilia Alberghina from the University of Milano–Bicocca, Italy, “There is a growing awareness in medical science that biological entities are systems; collections of interacting parts.”
But modelling the big picture must be tightly linked to experimental data if the results are to be meaningful, argues, Mathias Reuss from the University of Stuttgart, Germany. “It is no use flooding computers with ‘omic’ data [from the] genome, proteome, or metabolome, and expecting a data-driven miracle.”
Beyond the issue of selecting and controlling the data that feeds systems biology models there is a need to pull together the efforts of large numbers of investigators, says Roel van Driel from the University of Amsterdam and the Netherlands Institute for Systems Biology, and co-chair of the ESF Forward Look on Systems Biology.
According to van Driel, the tools for understanding the key processes of life are already within reach and in the next ten years systems biology will bring major benefits to society.
“Nevertheless,” he says, “progress is slow. The reasons are the extreme complexity of biological systems and the fragmented way biology research is carried out.”
To overcome this van Driel says, “We have to initiate large-scale, highly focused, goal-oriented and systematic international efforts concentrating on a limited number of carefully selected key issues in health and biotechnology.”
New life forms
As systems biology progresses, it will generate a knowledge base that is important for biotechnology, paving the way to a more predictable and rational approach to cellular and metabolic engineering, says Uwe Sauer of the Institute of Molecular Systems Biology at the ETH in Zurich, Switzerland. This opens up the possibility of synthesising new life forms from scratch, for example, microorganisms for use in the production of foodstuffs and chemicals, or plants with desirable traits.
To build realistic models of cells, tumours, or whole organisms and run them on a computer, scientists will want a mathematical tool box that can cope with complex behaviours. This means, “an entirely new mathematics will be needed,” argues Mats Gyllenberg, University of Helsinki, Finland.
Modelling cellular networks in space and time will also depend on a close collaboration with the engineering and physical sciences, adds Olaf Wolkenhauser from the University of Rostock, Germany.
However, the main bottleneck will remain the storage of masses of dynamic information, says Heikki Mannila from the Helsinki University of Technology. “By comparison, sequencing of the human genome was an easy task for information technology,” he says.
Standardising experimental techniques
One key to success will be standardising experimental techniques, thus avoiding the generation of conflicting data, says Ursula Klingmüller. For example, Germany’s HepatoSys consortium, which aims to build a complete model of liver function, agreed at the outset to use data from only one inbred mouse strain.
Adopting Systems Biology strategies could soon translate into innovative new medicines believes Adriano Henney, from the pharmaceutical company AstraZeneca plc, Cheshire, UK. Modelling and simulation, which so far have played a minor role in R&D, could enable companies to steer around some of the problems that lead to promising compounds failing clinical trials.
For the food and personal care giant Unilever, systems biology could allow safety decisions to be made without resorting to animal tests, says Janette Jones, who describes the company is currently working to integrate the results from protein microarrays into mathematical models as a test for skin sensitivity.
Results coming out of European programmes on mammalian cell cycle, tissue development and degeneration, stem cell differentiation, organelle function, and endocytosis are paving the way in this rapidly moving field. “The EU has emerged as a major world player in systems biology,” says Alfred Game of the Biological and Biotechnology Research Council in the UK. He claims that publicly funded research agencies in Europe are getting involved in initiatives that have been set up to better coordinated their activities such as ERA-SysBio.
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