Department of Bioinformatics
Head: Stefan Schuster
School of Biology and Pharmacy
Friedrich Schiller University, Jena, Germany
Metabolic Modeling
Alternative Splicing
- Reconstruction and structural analysis
- In many higher organisms mRNA is spliced before translation.
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, 433-441
[2] L.F. de Figueiredo et al. (2009) Can sugars be produced from fatty acids? A test case for
pathway analysis tools. Bioinformatics 25, 152-158
[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, 1872-1883
[4] L.F. de Figueiredo et al. (2009) Computing the shortest elementary flux modes in genomescale metabolic networks. Bioinformatics 25, 3158-3165
[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, 217-222.
-
[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
- Various patterns of microbial (inter)actions lead to different
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].
Modeling of
Biological Oscillations
- Many biological species possess a circadian clock, which helps
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]
-
-
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.
- 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, 312-318
[10] S. Schuster et al. (2010) Cooperation and cheating in microbial exoenzyme production Theoretical analysis for biotechnological applications. Biotechnology Journal 5, 751-758
Contact
[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, 316-334
[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
Collaboration
Local
- 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
http://pinguin.biologie.uni-jena.de/bioinformatik
[email protected] (secretary)
Ernst-Abbe-Platz 2, D-07743 Jena
(Jena School of Microbial
Intern
- Austrian Research Center, Vienna
- CEIT, Spain
- Oxford Brookes University, UK
- Tel Aviv University, Israel
- University of Bergen, Norway
- University of Birmingham, UK
and - University of Maribor, Slovenia