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What is systems biology?

Systems Biology in a nutshell

According to the definition adopted by the ERASysBio (European Research Area for Systems Biology) initiative, a consortium of funding agencies from 13 european and associated countries, "systems biology is a means of understanding the dynamic interactions between the components of a living system and, also, between living systems and their interactions with the environment. It is an approach by which biological questions are addressed through integrating experiments in iterative cycles with computational modelling, simulation and theory. Modelling is not the final goal, but it is a tool to increase understanding of the system, to develop more directed experiments and, finally, allow predictions. Intrinsic to systems biology is its interdisciplinary nature and the common aim of achieving the quantitative understanding of dynamic biological processes, through the use of mathematical and statistical analyses to integrate biological data, in order to develop predictive models of biological behaviour".

Systems biology is the common language and the transdisciplinary research strategy adopted for all the life sciences in the 21st century. It facilitates the integration of biology, medicine and environmental sciences through a variety of transdisciplinary interactions with mathematics, computer science, physics and engineering, allowing us to face up to the biggest challenges in science, technology, and society in general.

Contrary to numerous other scientific disciplines, research in biology has always been carried out in a fragmentary fashion with each laboratory mostly studying one specific phenomenon, often limited to only one cellular type from one organ and one species in any given environment. This approach in the life sciences developed because of the problems of data analysis, variability of measurements, and the absence of any laws that were considered to be universally applicable.

The unquestionable biological revolution of the 20th century was within the sphere of molecular biology. By providing extremely powerful and universal means of study, molecular biology firmly established itself as a discipline. Today, every hospital, every food processing, pharmaceutical or cosmetic industry, every ecological, legal or military organisation uses molecular biology to heal, protect, feed, grow, use, detect and understand living organisms. The progress made in more recent years has enabled us to apply molecular biology very widely, by analysing millions of molecules, by comparing species, and by studying life within the broad diversity of environmental conditions. In spite of this progress, why has the study of biology in the late 20th century remained so fragmentary? This limitation is due to the inability of classical biological approaches to tackle living systems in their entirety and, hence, to encompass their complexity. This complexity results from an extreme heterogeneity of components, an intrinsically dynamic nature, the spatial properties of the interactions between these components, and a highly non-linear behaviour system resulting from these interactions. It is impossible to comprehend the puzzles of life simply by studying the jigsaw pieces one by one.

Systems biology tackles this complexity with the rigour applied to other disciplines. It has become clear, now, for every biologist that the understanding of pathology or a biological process must involve the deciphering of a system of interactions that are dynamic (development and evolution), multivariate (measurements of millions of molecules and of multiple parameters) and multi-scale (from molecules to ecosystems, from milliseconds to millions of years). Systems biology is an approach tackling the complexity of biological systems and their dynamic behaviour at every relevant organizational level (from molecules, cells and organs through to organisms and ecosystems). It combines reductive and integrative methods whilst highlighting both the system components and the interactions between these components that, in turn, generate certain phenomena at a higher organizational level. This approach is revolutionizing biology because it provides an increased capacity and support for analysis in simulations, which have also undergone a revolution in approach thanks to the constant evolution of computing techniques.

These days, it is not more difficult to measure the activity of a whole genome than it is that of a single gene, or even to sequence the genomes of thousands of micro-organisms or hundreds of human beings. Microscopy now offers extremely high resolution so thousands of single cells can be analysed in parallel, the whole tree of life can be observed and medical science can analyse thousands of parameters for each patient. Confronted with this flood of data, biologists are often at a loss because experimental planning and analysis methods need to be adapted accordingly. By adopting the skills of various disciplines, systems biology can offer many different tools and solutions. However, it is not only data that is involved. The study of a living system relies on a multitude of parameters (half-life, diffusion speed, affinity etc.) that cannot all be measured experimentally. These days, biologists can apply computational or mathematical models that describe systems and lead to an understanding of their functioning. Systems biology aims to integrate, into an iterative process ("the virtuous circle"), the high-throughput of relevant data with a dynamic multi-scale modelling approach. It is important to note that building such models often requires the accumulation of relevant data that are not necessarily the type of data usually recorded by biologists. In particular, it is vital to obtain kinetic data which is rarely collected. The systems biology approach is not only a modelling approach but also an innovative experimental one.

It is essential to keep in mind that the main goal of systems biology is to extend our understanding of biological phenomena. However, to achieve this, the complexity of the problems raised always unveils new theoretical questions, sometimes very complicated, in associated, but non-biological, disciplines. Systems biology is situated at the interface between such disciplines and also poses eminently interesting questions within each area of research.