Master/Diploma students starting July 2013 or later
The group Genome Organization & Function at the BioQuant conducts several interdisciplinary research projects with funding from different sources. Our current research activities are described on the Publications and Research pages. We are looking Bachelor/Master/Diploma students (please contact us for projects) as well as PhD students and Post-docs with background/interest in either Molecular/Cell Biology, Physics or Computer Science.
PhD and Postdocs
Open positions in various research initatives (see our funding sources) are listed below under "Positions available". Alternatively, you may apply for PhD and Postdoc fellowships in various programs. As a group of the Deutsches Krebsforschungszentrum (DKFZ) we participate in the DKFZ International PhD Program, which offers 36 fellowships each year. Our group is part of the "Research Program B: Functional and Structural Genome Research". In addition, our group is a member of the Cluster of Excellence CellNetworks in Heidelberg and the HBIGS Graduate School of Molecular and Cellular Biology. Please feel free to contact us for further information on the the various PhD programs or other fellowship applications or positions available from third-party funding (DFG, BMBF etc.) of our research projects.
- DKFZ International PhD Program http://www.dkfz-heidelberg.de/en/phd-program/
- HBIGS international PhD program http://www.hbigs.uni-heidelberg.de/
- Boehringer Ingelheim Fonds http://www.bifonds.de/
- Schering Stiftung http://www.schering-stiftung.de/
- Fonds der Chemischen Industrie http://fonds.vci.de/
- Studienstiftung des deutschen Volkes
- Cluster of Excellence Cellular Networks http://www.cellnetworks.uni-hd.de
- DKFZ Post-doc program http://www.dkfz.de/en/postdoctoral-fellowship-program
- Daimler Benz-Stiftung
- AvH http://www.humboldt-foundation.de/
- Deutsche Krebshilfe http://www.krebshilfe.de/nachwuchsfoerderung.html
- Human Frontier Science Program http://www.hfsp.org
- Peter und Traudl Engelhorn-Stiftung http://ptes.2c4b.de/
Short term visits (3-6 months)
Postdoc/PhD positions currently available requiring a fellowship:
(contact: Karsten Rippe)
Epigenetic gene silencing networks (Postdoc/PhD student)
Start: Fall 2012
Project: Epigenetics is being recognized as pivotal to numerous fields of medical research including cancer, developmental diseases and the reprogramming of adult somatic cells into stem cells. The associated mechanisms are already being exploited for disease diagnosis and treatments by new generation of anti-cancer drugs. However, such drugs affect epigenetic modifications in the genome in complex and poorly understood ways. Thus, there is an urgent need for predictive models of epigenetic regulatory networks. Epigenetic regulation operates via DNA methylation, covalent modifications of histone tails and protein-protein/DNA interactions of histones and other chromosomal proteins. These factors control the DNA accessibility and thus gene transcription, DNA replication, repair and recombination. It is now emerging that the various epigenetic players interact in a complex and highly dynamic network to induce, propagate or reverse functional states of chromatin. To probe the underlying molecular mechanisms in living cells, we apply a combination of advanced in-vivo fluorescence microscopy and spectroscopy techniques. These are complemented by in-vitro studies using recombinant proteins that serve to precisely quantitate protein and nucleic acid interaction parameters like binding constants and association state. The goal is it to derive a quantitative description of a prototypic epigenetic networks that induces gene silencing. The work is being conducted within a consortium of several groups (see www.EpiSys.org) in the BMBF SysTec program.
Previous training: Candidates should have a master/diploma in Biology, Chemistry or Physics with a study focus on quantitative biology, biochemistry, biophysics or physical chemistry. Interest in interdisciplinary work is expected as well as knowledge/interest in one or more of the following areas: Quantitative/mechanistic analysis of molecular biological processes, chromatin organization and dynamics.
2. Jegou, T., Chung, I., Heuvelmann, G., Wachsmuth, M., Görisch, S. M., Greulich-Bode, K., Boukamp, P., Lichter, P. & Rippe, K. (2009). Dynamics of telomeres and promyelocytic leukemia nuclear bodies in a telomerase negative human cell line. Mol Biol Cell 20, 2070-2082. Abstract | Reprint (3.3 MB pdf file).
3. Müller, K. P., Erdel, F., Caudron, M., Marth, C., Fodor, B. D., Richter, M., Scaranaro, M., Beoudoin, J., Wachsmuth, M. & Rippe, K. (2009). A multi-scale analysis of dynamics and interactions of heterochromatin protein 1 in the nucleus by fluorescence fluctuation microscopy, Biophys. J. 97, 2876-2885. Abstract | Reprint (3.3 MB pdf file)
4. Erdel, F., Schubert, T., Marth, C., Längst, G. & Rippe, K. (2010). Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites. Proc. Natl. Acad. Sci. USA 107, 19873-19878. Abstract | Reprint (1.4 MB) | Commtent 1 | Comment 2
Mapping protein mobility and interactions in living cells by spatiotemporal fluctuation microscopy (Postdoc/PhD student)
Start: Fall 2012
Project: The cell nucleus is a highly dynamic place: proteins diffuse through the nucleoplasm, associate into complexes or interact with parts of the genome to regulate its function. To investigate these processes, the combination of fluorescence bleaching and correlation methods in conjunction with an integrative multi-scale analysis of the corresponding data sets is ideally suited. It allows the determination of parameters like intracellular concentration, association state, diffusion coefficient, kinetic binding and dissociation rate constants. When conducting these measurements in a spatially resolved manner protein mobility maps can be constructed that reveal local changes in genome accessibility and interactions for the proteins studied. To implement this approach a parallel data acquisition setup is highly advantageous. This is accomplished with our recently developed spatial and temporal fluctuation microscope (STFM). It is designed for fast confocal imaging and simultaneous fluorescence correlation spectroscopy measurements at hundreds of spots along a line. The advancements in data acquisition and analysis of protein mobility and interactions will be applied in the context of proteins involved in establishing and maintaining a repressive heterochromatin state as well as human chromatin remodeling complexes of the ISWI family.
Previous training: Candidates should have a master/diploma in Physics, Chemistry or Biology and interest in the advancement of fluorescence microscopy/spectroscopy techniques and associated data analysis.
References s. above
1. Heuvelmann, G., Erdel, F., Wachsmuth, M. & Rippe, K. (2009). Analysis of protein mobilities and interactions in living cells by multi-focal fluorescence fluctuation microscopy. Eur. Biophys. J. 38, 813-828. Abstract | Reprint (0.8 MB pdf file)
2. Erdel, F., Müller-Ott, K. P., Baum, M., Wachsmuth, M. & Rippe, K. (2010). Dissecting chromatin interactions in living cells from protein mobility maps. Chromosome Res. 19, advance online publicatione 17 September 2010. Abstract | Reprint (0.6 MB)
Integrative modeling of DNA sequence, epigenetic modifications and spatial chromatin organization (Postdoc/PhD student)
Start: Fall 2012
Projects: The different functional cell states are encoded by the DNA sequence, associated epigentic modificiations of the DNA and histone proteins and the accessibility of the DNA sequence information as determined by the spatial multi-scale organization of the genome. The interplay of these factors will be investigated by bioinformatics and computer simulation approaches. The ongoing projects involve the analysis of genome-wide sequencing data that reflect both (epi)genomic states and spatial organization to model nucleosome positioning and chromatin fiber folding via force field calculations, (steered) molecular dynamics and Monte Carlo procedures. The aim is it to integrate DNA sequence information, epigenetic modifications, chromatin structure and dynamics at different scales to explain its role in regulating gene expression. Results from the modeling work are tested and further refined against experimental data. Predictions will be developed on how biological factors can interact with chromatin to exert their function. The work is being conducted within a European consortium of several groups (see www.EpiGenSys.org) in the EraSysBioPlus program.
Previous training: Candidates should have a master/diploma/PhD in Physics or Computer Sciences. Interest in interdisciplinary work is expected as well as knowledge/interest in one or more of the following areas: Analysis of genome-wide DNA sequencing data, numerical simulations, quantitative/mechanistic analysis of molecular biological processes
2. Stehr, R., Schöpflin, R., Ettig, R., Kepper, N., Rippe, K. & Wedemann, G. (2010) Exploring the conformational space of chromatin fibers and their stability by numerical dynamic phase diagrams. Biophys. J. 98, 1028-1037. Abstract | Reprint (2.3 MB pdf file)
3. Teif, V. B. & Rippe, K. (2009). Predicting nucleosome positions on the DNA: combining chromatin remodeling activity with intrinsic binding affinities. Nucleic Acids Res. 37, 5641-5655. Abstract | Reprint (0.8 MB pdf file)
4. Kepper, N., Foethke, D., Stehr, R., Wedemann, G. & Rippe, K. (2008). Nucleosome geometry and internucleosomal interactions control the chromatin fiber conformation, Biophys. J. 95, 3692–3705. Abstract | Reprint (3.2 MB pdf file)
Synthetic epigenetic chromatin switches (Postdoc/PhD student)
Start: Fall 2012
Project: Current synthetic switches for gene expression in eukaryotic cells originate from prokaryotes. They rely on a specific DNA sequence that provides the binding site for a repressing or activating factor. The occupancy of these sites is then directly translated into the expression of a (regulatory) target gene. Some of these systems have been shown to work as synthetic toggle switches or hysteretic circuits in eukaryotes. However, gene regulation in eukaryotes is fundamentally different from prokaryotes: The eukaryotic genome is organized by histones and other chromosomal proteins into a nucleoprotein complex termed chromatin. In addition to signals encoded in the DNA sequence, post-translational epigenetic modifications (e.g. DNA methylation, post-translational histone modifications), non-coding RNAs and nucleosome positioning form a transcription regulation network. Due to the combinatorial complexity of this network a eukaryotic cell can adopt an enormous number of different epigenetic states that are preserved through cell division. This programming is fully reversible since the associated epigenetic pattern can be modified or completely erased and rebuilt. In the research project epigenetic chromatin switches will be constructed in vitro and in vivo in a synthetic biology approach.
Previous training: Candidates should have a background in Biophysics and/or Molecular Biology. Interest in interdisciplinary work is expected as well as knowledge/interest in one or more of the following areas: Quantitative/mechanistic analysis of molecular biological processes, chromatin organization and dynamics, gene regulation.
1. Erdel, F., Schubert, T., Marth, C., Längst, G. & Rippe, K. (2010). Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites. Proc. Natl. Acad. Sci. USA 107, 19873-19878. Abstract | Reprint (1.4 MB) | Commtent 1 | Comment 2
2. Rippe, K., Schrader, A., Riede, P., Strohner, R., Lehmann, E. & Längst, G. (2007). DNA sequence- and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes. Proc. Natl. Acad. Sci. USA 104, 15635-15640. Abstract | Reprint (1.4 MB pdf file) | Comment
4. Kepert, J. F., Mazurkiewicz, J., Heuvelman, G., Fejes Tóth, K. & Rippe, K. (2005). NAP1 modulates binding of linker histone H1 to chromatin and induces an extended chromatin fiber conformation. J. Biol. Chem. 280, 34063-34072. Abstract | Reprint (1.1 MB pdf file)