Systems biology concept

E. Klipp, R. Herwig, A. Kowald, C. Wierling, and H. Lehrach, Systems Biology in Practice Concepts, Implementation and Application, Wiley VCH Verlag GmbH, Weinheim, 2005. 

Toxicology is the study of the noxious effects of chemical and physical agents. The most fundamental concept in toxicology states that there is a relationship between the dose of an agent and the response that is produced in a biological system. The concept was first formalized by Paracelsus (1493-1541 A.D.). 

The concept of limitation is very attractive both for theorists and experimentalists. It is very useful to find conditions when a selected reaction step becomes the limiting step. We can change conditions and study the network experimentally, step-by-step. It is very convenient to model a system with limiting steps the model is extremely simple and can serve as a very elementary building block for further study of more complex systems, a typical situation both in industry and in systems biology. 

The continuous confrontation of model predictions with experimental results and vice versa is also a hallmark of most areas of natural science. Advanced mathematical concepts and methods have traditionally been considered less useful in the life sciences, partly, of course, because living systems are so much more complicated than most of the systems that we have been concerned with in physics and chemistry. However, this state of affairs is coming to an end. Today Systems Biology is considered as one of the most exciting areas of science, and many professional biological and physiological journals publish detailed model studies, side by side with purely empirical studies. 

Fig. 1 The integration of systems biology tools with metabolic engineering for advancing industrial biotechnology is herein referred to as industrial systems biology. Industrial systems biology offers the opportunity to introduce new concepts in metabolic engineering and advances the development of cell factories through traditional fermentation for production of natural products and, after the advent of recombinant DNA technology, for the production of recombinant metabolites [1]...

Systems-level approaches were defined more than 60 years ago with the application of general systems theory to various scientific fields including chemistry and life sciences with emphasis on morphogenesis (von Bertalanffy 1968 Friboulet and Thomas 2005). In the sixties, concepts derived from Ilya Prigogine s dissipative structures theory were also applied to biochemical oscillation and morphogenesis (Friboulet and Thomas 2005). In the seventies, numerical analyses of biochemical systems were developed which could represent a first step into modem systems biology (Hammer et al. 2004 Aderem 2005). 

Second, in terms of experimental design, concentration data for PK should be systematically collected. That may not seem terribly exciting but forms the basis for correct extrapolation. Those data should be analyzed with pharmacokinetic models to quantify the in vitro PK and transpose it (using well-developed PBPK concepts) to the whole body. To relate cellular levels to effects, empirical (statistical) dose-response models can be used, but systems biology models are probably more interesting and fruitful in the long run. 

Over the past decade or so, these remarkable achievements by nature have been recognized by the polymer science community. This has led to an increased interest in the use of biological concepts to synthesize polymers or to control the structure and properties of synthetic polymers. Of particular interest are peptide hybrid polymers. Combining peptide and synthetic polymer segments into a single macromolecule offers interesting possibilities to synergize the properties of the individual components and to compatibilize bio- and synthetic systems. 

Complex micellar systems like microemnlsions or special solid systems (suspensions or solid dispersions) nsn-ally require a basic pharmaceutical development strategy and sufficient understanding of the technical and biological concept to ensure appropriate quality, safety, tolerability, and reproducibility of the formulation. Such sophisticated systems can usually be properly elaborated only at later development stages also because of lacking of sufficient drug substance at early stages ... 

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