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Robust and sensitive: how cells keep themselves in balance


September 14, 2017

Networks in biological cells are subject to stress. They can collapse, like overloaded traffic or data systems. In a new study, researchers from Jacobs University and the University of Bremen examined the robustness of the interlinked networks of gene regulation and metabolism. This is the first time the theory of  interdependent  networks has been applied to biological cells.

The interdependencies between different infrastructural systems are a potential risk in our industrialized world. Train commuters know that faults in the local public transport system can affect the network of long-distance trains. There will be delays. A defect in one network negatively affects the directly dependent nodes in another network. Under certain circumstances, there can be system-wide cascades of perturbations, which can lead to the entire system breaking down. In statistical physics, such a point is called a percolation threshold.

Interdependent  networks are also present in biological cells. Investigating their operating principles is of high medical interest. Nonetheless, genes and metabolism, the two major networks of biological cells, are still largely seen as separate systems despite their strong interrelations and interdependencies.

What do cells need to remain robust if the genetic network, as a regulatory system, and the supply networks of metabolism are interdependent? In a cooperation between Jacobs University and the University of Bremen funded by the German Research Foundation, researchers have now been able to connect the findings from both networks. They analyzed the robustness of these  interdependent networks using the example of a biological model organism, the intestinal bacterium, Escherichia coli. The paper has now been published in the renowned scientific journal, Nature Communications.

“Our investigation is the first quantitative application of the theory of  interdependent  networks to biological cells,” says Marc-Thorsten Hütt, Professor of Computational Systems Biology at Jacobs University. Together with Dr. Anne Grimbs from Jacobs University and Professor Stefan Bornholdt’s team from the University of Bremen, Professor Hütt proved the existence of different percolation thresholds for perturbations present in different network regions. In this way, the system can fulfill all the conflicting requirements and quickly respond to changes in environmental conditions as well as being robust against systemic perturbations.

The investigation is based on a meticulous combination of several large databases on gene regulation and the metabolic reactions of Escherichia coli. Dr. Anne Grimbs was responsible for this part of the project. Jointly with David Klosik from Professor Bornholdt’s research group, who carried out the statistical analyses, Grimbs then formulated the modification of the percolation analysis to the biological system.

“Besides analyzing biological networks, my research group has for many years also analyzed networks from production logistics. In logistics, the balance between robustness and efficiency is, of course, a major issue. The interdisciplinary viewpoint has helped us gain a better understanding of the biological system here,” says Professor Hütt. For this reason, the researchers are hoping to find this balance of sensitivity and robustness in many other systems in which regulation (such as in the genetic network) and supply or production (as in the metabolic network) have an interdependent relationship.

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Questions will be answered by:
Prof. Dr. Marc-Thorsten Hütt | Professor of Computational Systems Biology
m.huett [at] | Tel.: +49 421 200-3238