Systems Biology is the scientific discipline of integrating experimental observations of biological systems with mathematical modelling to reveal new biological properties at the systems level. The comprehensive experimental observations of gene expression, protein and metabolite composition, metabolic flux distribution as well as interactions between the various cellular constituents are inputs for integrative data analysis and construction of mathematical models of the biological system under study.
The outcomes of the Systems Biology approach are development of predictive models of cellular behaviour and new insight into biological properties. It is believed that Systems Biology will have a major impact on how modern biological and biotechnological research is carried out, from development of microbial industrial bioprocesses to personalized medicine.
Department of Biotechnology, NTNU together with SINTEF Biotechnology has taken an initiative to establish Microbial Systems Biology in Trondheim. The basis for the initiative has been the study of two microbial systems, alginate production in Pseudomonas fluorescens and antibiotic production in Streptomyces spp. The NTNU-SINTEF partnership has over 15 years of experience in the molecular biology to bioprocess optimization of the two microbial systems.
In 2007 Department of Biotechnology will establish a permenant position in Systems Biology with research focus on data analysis and data integration that will complement existing competence in molecular biology, fermentation and analysis. This position is a part of a joint recruitment and establishment of Systems Biology research and education at the Faculty of Natural Sciences and Technology, NTNU since two other positions in Systems Biology are currently under establishment at Department of Biology and Department of Chemical Engineering.
Current and future research activities in Systems Biology
Department of Biotechnology and SINTEF Biotechnology have been successful and has been granted two projects in collaboration with european partners in the ERA-net research initiative SysMO (Systems Biology of Microorganisms) . The projects will start 1. March in 2007 and NTNU is in the process of recruiting personell at the post doc level.
The two SysMO project with a partner from Trondheim is:
Global metabolic switching in
SINTEF Biotechnology, Trondheim is partner in this project and professor Arne Strøm, professor Sergey Zotchev and associate professor Per Bruheim, all Department of Biotechnology, NTNU, will have active roles as scientific advisors for the norwegian partner in this SysMO-project. Other european partners comes from UK, Germany, Netherlands and Spain.
About the project
Streptomyces spp. are important industrial microorganisms since over 70% of clinically used antibiotics are produced by this microorganism. The antibiotics are not produced as part of the growth but in a post-growth phase called secondary metabolism. The main objective of this project is to explore the events that take place at gene expression-, protein-, metabolite-, and metabolic flux-levels during the transition phase from primary metabolism to secondary metabolism when the production of antibiotics starts. This will yield new information and knowledge of what triggers the onset of secondary metabolism and what controls the quantity of production of secondary metabolite. This knowledge together with development of predictive mathematical models should potentially benefit the development of new and commercially profitable secondary metabolite bioprocesses.
For further information about the norwegian contribution to this project contact: Research director Trond E. Ellingsen, SINTEF Biotechnology.
Systems Biology of a genetically engineered Pseudomonas fluorescens with inducible exo-po
Other norwegian partner in the project is SINTEF Biotechnology, Trondheim. European partners are professor Roy Goodacre, University of Manchester, UK, professor Uwe Völker, Ernst Moritz Arndt Universität, Greifswald, Germany, and professor Jens Nielsen, Technical University of Denmark, Denmark.
The main objective of the project is:
Systems Biology will be used to explore the dynamics and robustness of metabolic networks in genetically engineered Pseudomonas fluorescens bacteria in which the level of production of the industrially important and medically relevant exo-polysaccharide alginate can be controlled over a wide range. Targeted and random gene interruption mutants affected in alginate synthesis and mutants expressing modified levels of key enzymes will also be included in the studies.
The alginate production will be controlled by addition of an externally added inducer, and at maximum levels of induction more than 30% of the total sugar consumption will be channelled into alginate production. To reduce interpretation complexity the bacteria will be studied in continuous cultivations at steady-state conditions and through time-course induction experiments. The cellular responses to induction of alginate synthesis will be analyzed at the RNA, protein and metabolite levels, including metabolic flux analysis. Targeted mutations and a global screen of a transposon insertion library will be used to identify genes not known to affect alginate synthesis. A ‘Top-down’ strategy using novel evolutionary computing will be linked to a ‘Bottom-up’ strategy with construction of a genome-scale metabolic model for integrative omics analysis and whole cell simulations.
For further information contact: Professor Svein Valla, Department of Biotechnology, NTNU.