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Project
The growth of all organisms requires that the genome is accurately replicated and equally partitioned between two cellular progenies. In eukaryotes, the duplication of chromosomes, the separation of sister chromatids, and their segregation to opposite poles of the cell prior to cytokinesis are features of the cell cycle and grant maintenance of genomic integrity. Eukaryotic cells have evolved a surveillance mechanism for DNA segregation, the Mitotic Spindle Assembly Checkpoint (MSAC). This checkpoint blocks anaphase onset and prevents exit from mitosis until all chromosomes are properly attached and have aligned on the mitotic spindle. Its malfunction leads to cell death, generates aneuploidy, might facilitate tumorgenesis and aging , and might contribute to cancer.
The research focuses on modeling and simulation of the human's mitosis transition controls, the MSAC and the mitotic exit. Our modeling approaches base on biochemical reaction networks. We use In particular: Differential equations, stochastic simulation, evolutionary optimization, and three dimensional effects. |
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The MSAC, is the major cell cycle control mechanism in mitosis. It delays the
transition from metaphase to anaphase until all chromosomes are correctly aligned
at the metaphase spindle equator. In early metaphase, the chromosomes are not attached
to the spindle of microtubules, while in late metaphase most chromosomes are attached.
Once all kinetochores are attached, anaphase initiation is rapid. The subscript n denotes the number of chromosomes (e.g. n = 46 for human) |
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Publications
Peer-reviewed articles in international journals
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Bashar Ibrahim, Peter Dittrich , Stephan Diekmann, Eberhard Schmitt (2008)
Mad2 binding is not sufficient for complete Cdc20 sequestering in mitotic transition control (an in silico study)
Biophys Chem. 134, 93–100.
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Bashar Ibrahim, Eberhard Schmitt, Peter Dittrich , Stephan Diekmann, (2008)
In-silico study of kinetochore control, amplification, and inhibition effects in MCC assembly
BioSystems (In Press).
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Bashar Ibrahim, Stephan Diekmann, Eberhard Schmitt, Peter Dittrich (2008)
In-silico Modeling of the Mitotic Spindle Assembly Checkpoint
PLoS ONE, 3(2): e1555.
- Bashar Ibrahim, Peter Dittrich , Stephan Diekmann, Eberhard Schmitt (2007)
Stochastic effects in a compartmental model for mitotic
checkpoint regulation
JIB, 4(3):66.
Peer-reviewed articles in proceedings
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Hendrik Rohn, Bashar Ibrahim, Thorsten Lenser, Thomas Hinze, Peter Dittrich (2008)
Enhancing Parameter Estimation of Biochemical Networks by Exponentially Scaled Search Steps
In: E. Marchiori and J. H. Moore (Eds.), Proceedings of the Sixth European Conference on Evolutionary Computation, Machine Learning and Data Mining in Bioinformatics (EvoBIO), Napoli, LNCS 4973, pp. 177–187, Springer Verlag.
- Thorsten Lenser, Thomas Hinze, Bashar Ibrahim, Peter Dittrich (2007)
Towards Evolutionary Network Reconstruction Tools for Systems Biology
In: E. Marchiori, J.H. Moore, J.C. Rajapakse (Eds.), Proceedings of the Fifth European Conference on Evolutionary Computation, Machine Learning and Data Mining in Bioinformatics (EvoBIO), Valencia, LNCS 4447, pp 132-142, Springer Verlag.
For pdf or update see publications of the Group page |
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