BioSim is a project funded by the European Community under the 6th Framework program and was initiated on December 1, 2004. The objective of the network is to demonstrate how the use of modern simulation techniques through a deeper and more qualitative description of the underlying biological, pathological and pharmacological processes can lead to a more rational drug development process and an improved treatment of diseases such as cancer diabetes and depression. At the same time, the biosimulation offers the possibility of a reduction in the use of animal experiments.
Introduction
With 26 academic partners, nine small and medium sized enterprises, one large pharmaceutical company, and the regulatory agencies in Denmark, Sweden, Spain and the Netherlands, BioSim commands expertise in including genetics, biochemistry, cell biology, physiology, pharmacology on the biological side as well as pharmacokinetics, bioinformatics, complex systems theory, and software development on the technical side. Several of the leading groups have worked in the areas of 'biosimulation' and 'computational systems biology' for more than 30 years. The net includes hospital departments that perform experimental treatment of patients with cancer and Parkinson's disease.
The BioSim Network demonstrates how the use of advanced mathematical modelling and computer simulation can contribute to the development of effective and personalized treatments of different chronic progressive disorders and how the same approach can lead to a reduction of the costs and lead times associated with the development of new medicines. This may gradually allow a reduction in animal experiments.
Diabetes Efforts concentrate on the role of mutations that effect the ion channels of the insulin-producing beta-cells, on the genetic basis for the development of neonatal diabetes, on the study of human (as opposed to mice) pancreatic cells, on the mechanisms underlying the development of insulin resistance, and on the possible role of prenatal nutrition for the development of type-2 diabetes. Models are also developed to analyse the balance between fat and glucose metabolism and to describe the rate of absorption of different insulin variants.
Cancer In this area the network uses computer models of the cell cycle and of its coupling to the 24 h day-and-night rhythm to improve the treatment of patients with cancer. The use of chronotherapy implies that the administration of anti-cancer drugs is adjusted in accordance with the circadian rhythm of the patient. For certain forms of cancer this has been found to increase the efficiency of the drug by a factor of five. Efforts are also devoted to the development of new anti-cancer drugs.
Hypertension and cardiovascular diseases Activities area focus on the development of 3D heart models that can be used to test how a new drug affects the regularity of the heart rhythm. Work is performed to develop detailed models of the mechanisms by which the individual nephron of the kidney regulates the incoming blood flow and how neighboring nephrons interact.
Mental disorders and neuronal systems Work includes application of mathematical models to develop less invasive and demand-controlled electrical stimulation techniques for the treatment of Parkinson's disease. Modelling studies are performed to examine the effect of sleep deprivation in the treatment of depression, and bioinformatic approaches are applied to try to identify forms of depression on the basis of the information available from blood samples.
Methodological issues The area encompasses description of complex networks of oscillating biological units, studies of the mechanisms of temperature stabilization in biological feedback regulations, application of new methods of data analysis, and development of modeling software and biomedical search machines. The area includes application of new experimental techniques such as interference microscopy and surface enhanced Raman spectroscopy to study cellular processes.
Regulatory issues and dialogue with the public Testing in animal and human subjects is a necessary part of the development of new drugs. Such experiments clearly raises a number of complicated ethical issues that the use of simulation models may reduce. This requires that the regulatory authorities can evaluate computer models and accept them as part of the required documentation.
During the last five years the BioSim Network has published nine books and 800 scientific publications. The network has organized or co-organized 30 conferences and workshops, edited four issues of international journals, and trained about 130 PhD students. New National Centres in Systems Biology have been established in relation to the BioSim partners in Manchester, Warwick, and Edinburgh.