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## Centre for Integrative Systems Biology at Imperial College (CISBIC)

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NEW: The CISBIC project has a new home page : http://www.imperial.ac.uk/cisbic
Minutes and slides from the project meetings are still available from: http://www.doc.ic.ac.uk/bioinformatics/CISBIC/meetings

Aims:
Biological systems are made up of very large numbers of different components interacting at various scales. In the past, experimental analysis of any single component, such as a gene or its protein product, was extremely time consuming. Consequently a single laboratory could study only a handful of such components at any one time. This led to a conceptual framework in which a single trigger event (such as receptor ligation or protein phosphorylation) was assumed to result in a single effect, which in turn initiated a further effect and so on, in a simple linear pathway.
In reality, most genes, proteins and other components carry out their functions within a complex network of interactions. A single component can affect a wide range of other components, and a complicated combination of causes may need to be satisfied for a single effect. Typical networks have positive and negative feedback loops that regulate their operation. Consequently, a single component (such as a gene) rarely controls any particular biological function, and conversely any given component may influence many different functions.
The recent revolution in high-throughput technologies offers an exciting opportunity to study such complex biological systems as an integrated whole. The experimentalist is no longer restricted to a handful of molecules. Sequence analysis provides a comprehensive catalogue of all of the genes in an organism, and it is possible to measure simultaneously thousands, or tens of thousands, of individual genes, proteins and metabolites. At the same time, novel imaging technologies allow the dynamic visualization of the spatio-temporal distribution, evolution and interaction of key molecules in live cells. The next challenge in life sciences research is to move on from characterisation of individual components towards an understanding of higher order systems represented by multimolecular modules, whole cells, and intact organisms. This implies a shift from a study of linear pathways to that of complex networks.
To meet this challenge, modern science requires new conceptual frameworks. Complex data sets, and complex networks, can rarely be understood using intuition, or traditional biological tools. Instead, an interdisciplinary approach, involving techniques from the mathematical, computational, physical and engineering sciences is required. To be fully effective such an approach needs to repeatedly traverse an iterative cycle of collaborative interaction (see figure below).
For this to take place efficiently, a diverse range of experts from different disciplines need to be unified in an environment that encourages multidisciplinary research. We will do this by establishing a Centre for Integrative Systems Biology at Imperial College (CISBIC) which will draw on the many varied strengths of the institution and extended collaborations, and on its long tradition of crossing conventional subject boundaries.
We consider the main challenges for such a Centre to be:

- to demonstrate that the above cycle of hypothesis formulation, experimental investigation, predictive modelling, model validation and formulation of the next hypothesis delivers major biological insights into complex systems;
- to develop a core of multidisciplinary expertise which can champion this
- to introduce new technologies that enhance the quality and quantity of relevant data;
- to stimulate research and teaching of systems biology in Imperial College and in the wider research community.

Our strategy for developing such a Centre involves:

- providing facilities for the high-throughput methodologies coupled to robust data integration;
- developing versatile strategies for mathematical, statistical and computational modelling;
- tackling an exemplar biological problem of host-pathogen interaction;
- stimulating and pump-priming others, both within and outside Imperial College, to pursue a systems biology approach to a diverse range of problems;
- developing teaching and training programmes in systems biology at both undergraduate and postgraduate level;
- establishing national and international links with academic and industrial colleagues.

Principal Investigator:

- Prof. D. Young (Director of the Centre)

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Co-investigators:

- Prof. S.H. Muggleton (Director of Modelling)
- Prof. M.J.E. Sternberg
- Prof. A. Dell
- Prof. J. Stark
- Prof. B. Wren

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