Jena Centre for Systems Biology of Ageing – JenAge

The JenAge Centre aims to identify conserved transcriptional and metabolic networks activated by mild stress and to investigate their role in preserving functional integrity in old age. JenAge will use a multi-species approach to characterise network modulations by environmental, pharmacological, and life-style perturbations. In an iterative process, experimental data will be communicated to the analysis and modelling groups to generate testable hypotheses, which will in turn be validated by genetic and other manipulations in model organisms. Automatic text mining will be used to cope with the ever-increasing flood of age-related scientific documents in a systematic way and to generate plausible hypotheses on ageing and age-related diseases through text analytics. This textual information will be used, together with data from other databases and from the JenAge Centre, to set up a new public database on molecular, cellular, and organismic aspects of ageing. The general JenAge objective is to gain new insights into the complex interplay of maintenance and repair networks that govern the lifelong accumulation of damage and finally lead to age-related diseases and death. Overall, the knowledge acquired within this initiative will contribute to sustained health in an ageing society.

People:

• Jürgen Sühnel (Coordinator; Leibniz Institute for Age Research, FLI)
• Udo Hahn (FSU, Jena University Language and Information Engineering Lab)
• Michael Ristow (FSU, Institute of Nutritional Sciences, Dept. of Human Nutrition)
• Stefan Schuster (FSU, Dept. of Bioinformatics)
• Otto Witte (University Hospital Jena, Neurology)
• Reinhard Guthke (Leibniz Institute for Natural Product Research and Infection Biology, HKI)
• Alessandro Cellerino, Stephan Diekmann, Peter Hemmerich, Christoph Englert, Matthias Platzer (Leibniz Institute for Age Research, FLI)

Funding: BMBF

Modelling the circadian clock of Chlamydomonas reinhardtii and its influences on nitrogen (GoFORSYS Partner Project)

This project is devoted to the study of the circadian clock of the unicellular green alga Chlamydomonas reinhardtii by a systems biological approach combining modern experimental techniques with modelling and computer simulations. In particular, the project aims to produce genetically modified C. reinhardtii strains with improved nitrogen use and photosynthetic capacity specifically during day phase. Based on simulations using an in silico model regulatory genes involved in nitrogen metabolism and photosynthesis will be selected for genetic manipulation. The translation of the respective mRNAs will be put under circadian control. This approach will lead to a systems-theoretical view on this part of green algae physiology and will be instrumental in simulating, analysing, and interpreting the underlying complex metabolic and genetic systems.

Further information: GoFORSYS Partner Project website

People:

• Maria Mittag (FSU, Institute of General Botany and Plant Physiology)
• Stefan Schuster (FSU, Dept. of Bioinformatics)
• Oliver Ebenhöh (University of Aberdeen, Institute for Complex Systems and Mathematical Biology)

Funding: BMBF (Projektträger Jülich)

Dynamics and regulation of the metabolic balance in Escherichia coli (FORSYS Partner Project)

Growth of the classical model organism Escherichia coli is often accompanied by excretion of intermediary or even toxic metabolites – a phenomenon termed overflow metabolism. The project focuses on mathematical modelling of the overflow metabolism of E. coli that limits both biomass yield and the quality of biotechnologically important products. The regulation of various metabolic pathways in E. coli is studied by experimental and theoretical work. Data from metabolite, mRNA, and protein levels are integrated into comprehensive mathematical modelling. Interesting dynamic phenomena such as oscillations will be investigated experimentally and by model simulations.

Further information: FORSYS Partner Project website

People:

• Reinhard Guthke (Coordinator; Leibniz Institute for Natural Product Research and Infection Biology, HKI)
• Michael Pfaff (BioControl Jena GmbH)
• Stefan Schuster (FSU, Dept. of Bioinformatics)
• Ursula Rinas (Helmhotz Centre for Infection Research, Braunschweig)
• Knut Jahreis (University of Osnabrück)
• Katja Bettenbrock (Max Planck Institute for the Dynamics of Complex Technical Systems, Magdeburg)
• Andreas Kremling (Technische Universität München)

Funding: BMBF

ERASysBio+ LINCONET
Modelling the gene regulatory network underlying lineage commitment in human mesenchymal stem cells: Identification of drug targets for the anabolic treatment of degenerative disorders.

To understand the mechanisms of stem cell differentiation is crucial in order to develop novel therapies for the regeneration of damaged tissues resulting e.g. from osteoporosis or rheumatoid arthritis. Basic questions are: Which genes govern lineage-specific differentiation, which are affected by the disease, and which genes are involved in tissue destruction? Given the complexity of the signalling systems governing disease development and progression, a systems biological approach is essential to understand these processes. Hence, the project aims to identify genes affected by tissue degeneration processes and to gain comprehensive understanding of tissue regeneration.

People:

• E. J. van Zoelen (Project coordinator; FNWI Radboud University, Nijmegen, NL)
• F. Falciani (University of Birmingham, UK)
• R. Guthke (Leibniz Institute for Natural Product Research and Infection Biology, HKI)
• R. W. Kinne (Experimental Rheumatology Unit, University Hospital Jena)