Molecular and Cellular Evolution (Prof. Dr. Hanspeter Herzel)
Statistical Analysis of DNA and Protein Sequences
The number of known DNA and protein sequences is growing extremely fast. Building on methods from statistical physics (correlation functions, mutual information, entropies), statistical dependences in sequences are analyzed. It has been shown, for instance, that certain statistical properties of the mutual information function of DNA sequences are universal, i.e. they are the same for different taxonomic classes (vertebrates, invertebrates, plants). Periodicities of 10-11 basepairs in complete genomes point to the supercoiled state of the DNA: negative supercoiling in eubacteria and positive supercoiling in archaea.
High density DNA-arrays ("DNA Chips") allow measurements of gene expression levels for a large number of genes simultaneously. In this way thousands of mRNA concentrations can be analyzed in parallel, potentially revealing complex gene regulatory networks. In close collaboration with cell biologists at the Charité(C. Sers, R. Schäfer) we assess the data reliability (image analysis, calibration, reproducibility), identify co-regulated genes by cluster analysis, and detect transcription factor binding sites in clusters of co-regulated genes. It is our aim to incorporate the resulting information into network models of signaling cascades such as the Ras pathways.
Biomedical Applications of Nonlinear Dynamics
Periodic and complex oscillations play a central role in biological systems. Examples include physiological rhythms (heartbeat, respiration, blood-pressure waves), neural oscillations and sound generation for acustical communication. Nonlinear dynamics theory has led to a detailed understanding of attractors, bifurcations and phase-response-curves. Irregularities in biological systems can partially be interpreted as a signature of deterministic chaos, and instabilities of parameters may be understood as bifurcations of the underlying dynamical systems.
The study of vocal fold oscillations is performed in close collaboration with the National Center for Voice and Speech of the USA and the university hospitals Universitätsmedizin Charité Berlin and Erlangen. Together with the experimental biologist W.T. Fitch (Vienna) nonlinear phenomena (subharmonies, biphonation, chaos) are studied in human and animal vocalization.
Systems Biology of the Circadian Clock
Together with the experimental group of Achim Cramer (Charité) we investigate the generation and synchronization of circadian rhythms on three different levels:
- Modeling intracellular feedback regulation in the core clock oscillator
- Studying the entrainment, synchronization and splitting of SCN neurons
- Bioinformatic analysis (high-throughput data, promoter studies, epigenetics) of phase- and tissue specificity of clock-controlled genes