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Systems Biology poised to revolutionize the understanding of cell function and disease

Systems Biology is transforming the way scientists think about biology and disease. This novel approach to research could prompt a shake up in medical science and it might ultimately allow clinicians to predict and treat complex diseases such as diabetes, heart failure, cancer, and metabolic syndrome for which there are currently no cures.

The European Science Foundation (ESF) has published a Forward Look (FL) report System Biology: a grand challenge for Europe; an attempt to identify how research in Systems Biology could be accelerated and developed further in Europe. The report concludes with a set of specific recommendations that aims at consolidating Systems Biology efforts in Europe. The idea of this ESF initiated FL first came to light with a proposal by the Netherlands Organization for Health Research and Development (ZonMw) and the NWO Council for Earth and Life Sciences in the Netherlands. The proposal was later materialised into concrete effort based on extensive discussions during a number of focused workshops and meetings between scientists and policy makers from academia and industry.

The report, which includes 12 essays from the scientific experts in academia and industry, illustrates Europes potential to be at the forefront of pinpointing the system causes of diseases, according to Dr. John Marks, the chief executive of the ESF.

The report tells us 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, adds Marks.

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.

Mathias Reuss from the University of Stuttgart, Germany, warns that modelling the big picture must be tightly linked to experimental findings. It is no use flooding computers with omic data genome, proteome, metabolome and expect a data-driven miracle.

The tools for understanding the key processes of life are already within reach, argues Roel van Driel from the University of Amsterdam and Netherlands Institute for Systems Biology and co-chair of the ESF Forward Look on Systems Biology. In the next 10 years, he predicts, it will bring about major benefits to society. But success will depend on the cooperative efforts of large numbers of investigators rather than on individual research groups.

As Systems Biology progresses, it will be possible to synthesise new life forms from scratch. Uwe Sauer of the Institute of Molecular Systems Biology, ETH, in Zurich, Switzerland believes that a systems-perspective, rather than the current gene-centric view, could open up entirely new options for the production of chemicals, food products and in plant breeding.

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. An entirely new mathematics will be needed, insists 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. But the main bottle-neck will be the storage of the masses of dynamic information, says Heikki Mannila from the Helsinki University of Technology and University of Helsinki, Finland. By comparison, sequencing of the human genome was an easy task for IT, he admits.

Ursula Klingmller, from the Systems Biology of Signal Transduction Group, DKFZ, in Heidelberg, Germany insists that the road to success will depend on standardising experimental techniques to avoid conflicting data. The HepatoSys consortium, for instance, that models liver function, agreed at the outset to use data from only one inbred mouse strain.

For pharmaceutical companies, adopting Systems Biology strategies could soon translate into innovative new medicines, Adriano Henney, from AstraZeneca, Cheshire, U.K. believes. Modelling and simulation, which so far have played a minor role in R&D, could avoid some of the pitfalls that result in promising compounds failing at the clinical trial stages.

At Unilever, a producer of food and personal care products, Systems Biology could allow safety decisions to be made without resorting to animal tests. According to Janette Jones and U.K. colleagues at Unilever, the company is currently investigating how to integrate the results from protein microarrays or chips into mathematical models as a test for skin sensitivity.

Embracing Systems Biology could boost a companys profits, says John Savin of Wendover Technology in the U.K. Not only will software-based technology cut the risk of therapeutics failing at the clinical stages, but discarded drugs could be revived by understanding what went wrong and possibly overcome the problem. As a result, computer modelling will become a mainstream tool in the pharmaceutical and biotech industries, he predicts.

Knowledge emanating from European-wide 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 from the BBSRC in Swindon, U.K. Already, research agencies in Europe have engaged in the ERA- SysBio, an ERA-NET set up to better coordinate their activities in this area.

The new report is the outcome of the ESF Forward Look on Systems Biology that has been conducted in 2004 and 2005. The recommendations were first published in the ESF Science Policy Briefing No. 25 in October 2005 -

In a further proof of how much the ESF values the importance and potential of Systems Biology, the organisation has invited renowned scientific leaders to offer their expertise on how to best implement the Forward Look reports recommendations. This Task Force, comprising of nine experts in the field, will publish a series of precise recommendations on necessary steps to accelerate research on Systems Biology in Europe based on the Forward Look report Systems Biology: a Grand Challenge for Europe on 10 September 2007 at

Recommendations from the report:

To meet this grand challenge for Europe,

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 (ERLs) - A cost-effective coordination of a European Systems Biology programme, as proposed here, requires a consortium of European Reference Laboratories (ERLs). ERLs are research institutes 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 proposed here will require an integrative and larger-scale level of funding than provided by grant systems now. We propose that a new financial model is developed based on cooperation between academies, 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 monodisciplinary teaching systems in Europe.

6. Cooperation between different European Systems Biology initiatives - As this Forward Look was initiated in 2004, Systems Biology was still in its infancy in Europe. In the mean time, however, a wide range of initiatives and funding programmes has started, both at the national and the European level.


Contact: Thomas Lau
European Science Foundation

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