1. Department of Bioinformatics
Head: Stefan Schuster
School of Biology and Pharmacy
Friedrich Schiller University, Jena, Germany
Metabolic Modeling
Alternative Splicing
- Reconstruction and structural analysis of metabolic networks aim at the identification of biochemical functional properties with applications in - Biochemistry (e.g. evolution of metabolism [1], pathway prediction [2]) - Biotechnology (e.g. strain optimization) - Medicine (e.g. age research, nutrition, enzymopathies).
- We develop new computational methods for analysis and integration of experimental data in large-scale networks [3,4].
- We use dynamic optimization approaches to study the regulation of metabolic pathways [5].
[1] J. Behre et al. (2008) Structural robustness of metabolic networks with respect to multiple knockouts. J theor Biol 252,
[2] L.F. de Figueiredo et al. (2009) Can sugars be produced from fatty acids? A test case for pathway analysis tools. Bioinformatics 25,
[3] C. Kaleta et al. (2009) Can the whole be less than the sum of its parts? Pathway analysis in genome-scale metabolic networks using elementary flux patterns. Genome Res 19,
[4] L.F. de Figueiredo et al. (2009) Computing the shortest elementary flux modes in genome- scale metabolic networks. Bioinformatics 25,
[5] M. Bartl et al. (2010) Just-in-time activation of a glycolysis inspired metabolic network - solution with a dynamic optimization approach. In: Proc. 55th International Scientific Colloquium. Ilmenau, Germany,
- In many higher organisms mRNA is spliced before translation. During this process, introns are cut out and the remaining exons are translated into a protein. - Alternative splicing can optionally lead to, e.g., retained introns or exons that are spliced out. The choice often depends on the tissue and the stage of development. - We examine different facets of alternative splicing:
- Analysis of how widely alternative splicing is spread in the fungal domain and which processes in the microbial lifestyle are affected [6] - Phenomenon of alternatively spliced eukaryotic transcripts with mutual exclusion of exons, where two splicing reactions depend on each other [7] - Alternative splicing at competitive tandem donor splice sites, where the splice site is shifted 4 nucleotides and in this way the reading frame changes [8].
[6] K. Grützmann et al. (2010) The alternative messages of fungal genomes. GCB Braunschweig
[7] M. Pohl et al. (2009) Mutually exclusive spliced exons show non-adjacent and grouped patterns. GCB Halle
[8] R. Bortfeldt et al. (2008) Comparative analysis of sequence features involved in the recognition of tandem splice sites. BMC Genomics 9, 202
Evolutionary Game Theory
and Agent-Based Modeling
Modeling of
Biological Oscillations
- Various patterns of microbial (inter)actions lead to different payoffs (survival, replication and distribution) under diverse environmental conditions. Thus, individuals can be assigned to players in a game (Evolutionary Game Theory) or to agents acting according to certain rules in a predefined environment (Agent-Based Modeling).
- Polymorphism of the fungus Candida albicans as survival strategies inside a macrophage leads to different evolutionary stable populations depending on switching costs. [9]
- Strategies like ‘cooperation’ and ‘cheating’ can be observed in yeasts. Examples are ATP production and the external hydrolysis of sucrose by invertase secretion. [10]
[9] S. Hummert et. al. (2010) Game theoretical modelling of survival strategies of Candida albicans inside macrophages. Journal of Theoretical Biology 264,
[10] S. Schuster et al. (2010) Cooperation and cheating in microbial exoenzyme production - Theoretical analysis for biotechnological applications. Biotechnology Journal 5,
- Many biological species possess a circadian clock, which helps them anticipate daily variations in the environment. The rhythm persists autonomously with a period of approximately 24h. Single pulses of light, nutrients, chemicals, or temperature can shift the clock phase.
- Circadian clocks are temperature compensated, thus the period of the circadian rhythm remains relatively constant within a physiological range of temperatures.
- Using sensitivity analysis, we theoretically investigate signaling properties, adaptations and entrainment in general oscillatory systems, such as calcium oscillations [11], circadian clocks [12,13] and the circadian regulated nitrogen metabolism of Chlamydomonas reinhardtii.
[11] C. Bodenstein et al. (2010) Using Jensen's inequality to explain the role of regular calcium oscillations in protein activation. Physical Biology 7:036009
[12] T. Hinze et al. (2010) Modelling Signalling Networks with Incomplete Information about Protein Activation States: A P System Framework of the KaiABC Oscillator. Lecture Notes in Computer Science 5957,
[13] T. Hinze et al. (2011, accepted) Synchronisation of Biological Clock Signals: Capturing Coupled Repressilators from a Control Systems Perspective. Proceedings of the Fourth International Conference on Bio-Inspired Systems and Signal Processing, IEEE Engineering in Medicine and Biology Society
Contact
Local Collaboration International
- Austrian Research Center, Vienna
- CEIT, Spain
- Oxford Brookes University, UK
- Tel Aviv University, Israel
- University of Bergen, Norway
- University of Birmingham, UK
- University of Maribor, Slovenia
- Fritz Lipmann Institute, Jena
- Hans Knöll Institute, Jena
- Max Planck Institute for Chemical Ecology
- Max Planck Institute of Molecular Plant Physiology
- Technische Universität llmenau
The department is a member of and
(Jena School of Microbial Communication).
(secretary)
Ernst-Abbe-Platz 2, D Jena