بورس دکتری آلمان Computational Systems Biology
Humboldt-Universität zu Berlin
DFG Research Training Group “Computational Systems Biology”
Biology has developed into a quantitative, information-driven science. We are seeking doctoral students for the DFG-funded Research Training Group “Computational Systems Biology” (CSB) which focuses on the system-level understanding of biological data using computational methods. CSB is embedded in the thriving Berlin life-science environment and involves high-ranking research institutions such as Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité-Universitätsmedizin Berlin, Max Planck Institute for Molecular Genetics and Max Delbrück Center for Molecular Medicine Berlin-Buch.
We are looking for highly-motivated students with a strong interest in systems biology and mathematical modelling. Successful applicants must hold the equivalent of a master’s level degree in life sciences, mathematics, biophysics or computer sciences. The PhD positions are offered for 3 years. The salary is according to the German TV E13 scale (65%).
We offer an excellent training program in computational systems biology, supervision by at least two experienced scientists, and multifarious opportunities for developing local and international collaboration.
Email contact: [email protected]
Application deadline August 5, 2016
Three positions are available – one in each of the following groups:
Non-genetic origins of cell-to-cell variability
Prof. Martin Falcke, Max Delbrück Center for Molecular Medicine
Cytosolic Ca2+ is a universal second messenger controlling a large variety of processes from egg activation after fertilization, gene expression and differentiation, secretion, muscle contraction etc. to cell death (1-5). One temporal form of Ca2+ signals are Ca2+ spike sequences, which control among other effectors also transcription under the control of NFAT, NFκB, STAT3, Oct/OAP (6-10). In recent years, our group has characterized the temporal properties of Ca2+ spike sequences. The main results are: Interspike Intervals (ISIs) are random with a linear relation between SD and average ISI (11-13), spike amplitude and duration are independent from stimulation in many cells, the average ISI exhibits an exponential concentration response curve. The randomness of Ca2+ spike timing and the observation of SDs of ISIs in the same order of magnitude as the average ISI render Ca2+ spiking a likely source of intrinsic noise and non-genetic origin of cell-to-cell variability. We will follow up this hypothesis by modelling the control of transcription by Ca2+ via the above transcription factors. We will also seek an experimental partner able to monitor expression of a reporter gene controlled by Ca2+ to obtain specific experimental results to be modeled.
- M. Berridge, Inositol trisphosphate and calcium oscillations. Biochem Soc Symp 74, 1 (2007).
- M. J. Berridge, Inositol trisphosphate and calcium signalling. Nature 361, 315 (1993).
- M. J. Berridge, Inositol trisphosphate and calcium signalling mechanisms. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1793, 933 (2009).
- M. J. Berridge, M. D. Bootman, P. Lipp, Calcium–a life and death signal. Nature 395, 645 (1998).
- M. J. Berridge, P. Lipp, M. D. Bootman, The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1, 11 (2000).
- R. E. Dolmetsch, R. S. Lewis, C. C. Goodnow, J. I. Healy, Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386, 855 (1997).
- R. E. Dolmetsch, K. Xu, R. S. Lewis, Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392, 933 (1998).
- S. Feske, J. Giltnane, R. Dolmetsch, L. M. Staudt, A. Rao, Gene regulation mediated by calcium signals in T lymphocytes. Nat Immunol 2, 316 (2001).
- L. Zhu et al., Ca2+ oscillation frequency regulates agonist-stimulated gene expression in vascular endothelial cells. J Cell Sci 121, 2511 (2008).
- L. Zhu et al., Cumulated Ca2+ spike duration underlies Ca2+ oscillation frequency-regulated NFκB transcriptional activity. Journal of Cell Science, 2591 (2011).
- A. Skupin et al., How does intracellular Ca2+ oscillate: By chance or by the clock? Biophys J 94, 2404 (2008).
- K. Thurley, M. Falcke, Derivation of Ca2+ signals from puff properties reveals that pathway function is robust against cell variability but sensitive for control. Proc Natl Acad Sci USA 108, 427 (2011).
- S. Dragoni et al., Vascular endothelial growth factor stimulates endothelial colony forming cells proliferation and tubulogenesis by inducing oscillations in intracellular Ca2+ concentration. STEM CELLS 29, 1898 (2011).
Gene regulatory mechanisms and networks
Prof. Martin Vingron, Max Planck Institute for Molecular Genetics
The Vingron group works on computational and data analytic approaches to gene regulation. Recently, we have applied network construction methods to epigenetic data and have developed new, non-linear network reconstruction methods (see 1-5 below). Such networks, together with a better understanding of functional chromatin segments, should allow us to gain insight into gene regulatory mechanisms. We are looking for a PhD student to contribute to our effort to model gene expression based on available data on transcription factor binding, epigenetic marks, and sequence features.
- Karlic R, Chung HR, Lasserre J, Vlahovicek K, Vingron M (2010) Histone modification levels are predictive for gene expression. Proc Natl Acad Sci U S A 107:2926-2931
- Lasserre J, Chung HR, Vingron M. (2013) Finding associations among histone modifications using sparse partial correlation networks. PLoS Comput Biol. 2013;9(9):e1003168.
- Perner J, Lasserre J, Kinkley S, Vingron M, Chung HR (2014) Inference of interactions between chromatin modifiers and histone modifications: from ChIP-Seq data to chromatin-signaling. Nucl. Acid Res. 42(22):13689-95
- Ghanbari M, Lasserre J, Vingron M (2015) Reconstruction of Gene Networks Using Prior Knowledge. BMC Syst. Biol. 9:84. doi: 10.1186/s12918-015-0233-4
- Mahsa Ghanbari, Julia Lasserre, Martin Vingron (2016) The Distance Precision Matrix: computing networks from nonlinear relationships. arXiv:1605.03378
Integrated analysis of metabolic and signaling processing in tumor cells
Dr. Jana Wolf, Research Group Leader, Mathematical Modelling of Cellular Processes, Max Delbrück Center for Molecular Medicine
In the last decade a number of tumor entities have been intensively analyzed. It has been shown that beside perturbations in signal transduction and gene regulation events, tumor cells harbor perturbed metabolic pathways. Characteristic is a shift in the cellular energy metabolism, leading to an enhanced glycolysis in the presence of oxygen (Warburg effect). However, other metabolic pathways are also modified. We are interested in an integrated understanding of the dysregulation of metabolic processes in neuroblastoma, which according to a long-term perspective, should be linked to perturbations in signaling processes.
منبع: Humboldt University of Berlin
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