Most of the diseases which plague humankind today are multifactorial: they are not simply the result of one mutation in one gene, producing one rogue protein that can no longer carry out its job. Diabetes and obesity, for instance, depend on many simultaneous genetic and environmental factors.
Similarly, in biotechnology, processes cannot be optimised by simply changing one component of a complex process. It is the networks of interaction that Systems Biology, the study of how biological networking produces function at the level of the cell, organ and body, focuses on. The idea is that once we know which networks are fired in health, and misfired in disease, we will know how to fix the consequences of misfires by treating networks rather than just component molecules.
The situation is much like that of hooliganism in a soccer stadium, explains Professor Hans Westerhoff, who splits his time between the Manchester Centre for Integrative Systems Biology, Manchester, U.K. and the Netherlands’ Institute for Systems Biology in Amsterdam and is a member of the ESF Task Force. If one person – or molecule – incites a person who then incites the next, then the whole crowd will misbehave. To deal with this, one should moderate the network, by making sure the individuals are too far apart to interact.
Systems Biology requires the integration of precise mathematical and experimental approaches, in ways and to extents that are new to mainstream Biology and Medicine. Europe leads in most of these individual approaches, but Systems Biology of any particular disease requires the simultaneous study of all the links in huge networks, and the best scientists for each of the different links are in different European countries.
For Europe to take its lead in the research of Systems Biology, the continent needs to establish an interactive network itself, meaning that nations should not independently address their own parts of the ‘grand challenge’ of Systems Biology. A paradigm shift is needed therefore, away from isolated, country-based, molecular biology and physiology, to extensive and intensive networks of excellent scientists across Europe.
The European Science Foundation (ESF) Task Force, comprising of nine experts in the field, has published a series of recommendations build on the ESF Forward Look report Systems Biology: a Grand Challenge for Europe . In their Strategic Guidance and Recommendations they set out a road map to establish a pioneering Systems Biology research programme in Europe. Based on the advice given by the Task Force the next steps will be to start actual discussions among the ESF’s 75 Member Organisations, the Commission and other actors in the field, both public and private, on how to go forward.
The vision is that Europe will take the lead in making a ‘blue cell’ — a generic, model blueprint of a cell — and then fill out the blueprint with information for a number of important diseases and biotechnological processes.
One prerequisite for this is new, much more quantitative, and biology-specific technology. A massive initiative is needed to develop the kinds of advanced technology that can look at networks in cells, clusters of cells, organs and bodies.
“We cannot move forward in Systems Biology in Europe unless we have the technology to back up our vision,” says Professor Rudolf Aebersold from the Institute of Molecular Systems Biology at ETH in Zurich, Switzerland, and a member of the ESF Task Force. “We need new, powerful, user-friendly technologies not only to process and integrate large amounts of data, enhance data sharing and visualise models of biological systems, but also to collect that data in the first place.”
Though the ultimate goal is applying Systems Biology to human health, to begin with it is likely that technology will also be developed and tested in smaller organisms and then scaled up to humans. Equally, the Task Force recommends that to begin with, particular topics on a common theme are chosen, such as cancer or obesity, and generic technology is produced that can then be applied to other areas.
To organise research in Europe, the Task Force recommends dividing funded research into two sub-themes: Systems Biotechnology and Multifactorial Diseases. These should be connected to, and incorporate, existing research programmes in Europe.
To achieve these goals, a massive workforce from many difference disciplines will be needed.
“We need scientists that can understand both sides of the Systems Biology coin: biologists that can handle equations and physical scientists that know their way around in experimental biology,” says Professor Westerhoff. “The Task Force recommends that more support is given to existing Systems Biology training and exchange programmes so that scientists from other disciplines are attracted to our field.”
The Europe-wide network will also need ‘hubs’; European reference laboratories allowing any researcher to conduct high quality research, even if their home institution cannot support it. These should also distribute standard experimental procedures, samples and datasets to ensure that everyone in the network is working in the same way. Similarly, Institutes of Advanced Studies should be established to host short-duration, focused programmes for researchers from across Europe.
The Task force has also suggested the ESF should support the overseeing of this network by continuing to support and host the establishment of a consortium of interested parties and support a European Systems Biology Office.Recommendations
The task force will then:
Initiate, coordinate and fund a single GRand Action on Systems Biology (GRASB), consisting of activities working towards the integral ‘Networks for Life’ project and become the world’s largest, best integrated, hence most effective Systems Biology programme.
Call for applications and expressions of interest in developing technology for and in carrying out world-leading Systems Biology research; a network of research on Systems Biotechnology; a network of research on multifactorial disease; a network of training activities; a network of European Reference Laboratories; and one or two Centres for Advanced Studies.
Organise workshops to ensure activities are kept up to date.
Develop a programme for GRASB, including funding mechanisms.
Define ways of disseminating strategies for all GRASB activities.
Thomas Lau | European Science Foundation
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