Approaching the three-dimensional organization of the human genome
To approach the still largely unknown sequential and three-dimensional organization of the human cell nucleus, the structural-, scaling- and dynamic properties of interphase chromosomes and cell nuclei were simulated on the 30 nm chromatin fiber level with Monte Carlo, Brownian Dynamics and parallel computing methods. Differences between used models explain various experimental conditions, favouring a Multi-Loop-Subcompartment model with 63-126 kbp loops aggregated to possibly rosettes connected by 63-126 kbp linkers, and predict correctly the transport of molecules by moderately obstructed diffusion excluding the Interchromosomal Domain hypothesis. Correlation analyses of completely sequenced Archaea, Bacteria and Eucaria chromosomes revealed fine-structured positive long-range correlations due to codon, nucleosomal or block organization of the genomes, allowing classification and tree construction. By construction and expression of fusionproteins from the histones H1, H2A, H2B, H3, H4 and mH2A1.2 with the autofluorescent proteins CFP, GFP, YFP, DsRed-1 and DsRed-2 the chromatin morphology could be investigated in vivo during interphase, mitosis or apoptosis and revealed different interphase morphologies for cell lines quantifiable by scaling analyses. Finally, construct conversions in simultaneous co-transfections due to recombination/repair/replication were discovered in 25 % of cells and led to a variety of new applications.
| Autor: | Knoch, Tobias Aurelius |
|---|---|
| ISBN: | 9783000099595 |
| Auflage: | 4 |
| Sprache: | Englisch |
| Seitenzahl: | 280 |
| Produktart: | Kartoniert / Broschiert |
| Verlag: | Knoch, Tobias, Dr. |
| Veröffentlicht: | 01.01.2011 |
| Untertitel: | Structural-, scaling- and dynamic-properties in the simulation of interphase chromosomes and cell nuclei long–range correlations in complete genomes, in vivo analysis of the chromatin distribution construct conversions in simultaneous co–transfections. |
| Schlagworte: | Monte Carlo genome organization histones homologous recombination interphase cell nucleus in vivo labelling nucleoplasma phylogenetic trees repair scaling/fractal analysis |
Dr. Tobias A. Knoch was born as son of Wolfgang F. Knoch and Waltraut Knoch née List on 19th May 1971, in Mannheim, Germany. After four years of primary school, he attended the Lieselotte-Gymnasium Mannheim from 1982 to 1991, receiving the Abitur as primus (1991). From 1991 to 1992, he served at the Central Army Group (CENTAG), Heidelberg. From 1992 to 1998 he studied physics, mathematics and biology at the Ruperto-Carola University, Heidelberg: After the Vordiplom in Physics (1994) and in Mathematics (1994), he received his Diploma in Physics with the thesis "Three-Dimensional Organization of Chromosome Domains in Simulation and Experiment" (1998) in the group of Prof. Dr. Jörg Langowski, Biophysics of Macromolecules, German Cancer Research Center (DKFZ), Heidelberg. There he also conducted his dissertation presented here from 1998 to 2002. Since 2002, he build up the international interdisciplinary group Biophysical Genomics at the Erasmus Medical Center, Rotterdam, The Nether- lands, and was a member of the Kirchhoff Institute for Physics in Heidelberg and is also a member of the BioQuant Center/DKFZ. Since 2007 he is Assistant Professor at the Erasmus Medical Center.His work resulted in several patents and publications. He is founder, head, coordinator, and reviewer of several international interdisciplinary cooperative networks and consortia. Honourably, he received: nine prizes for excellent achievements at the Lieselotte-Gymnasium, the scholarship from the Studienstiftung des Deutschen Volkes, Bonn, awards of the Molecular Graphics and Modelling Society, San Diego (1998), and of the German Cancer Research Center (DKFZ, 1999), as well as the Klaus Goerttler Prize of the German Society for Cytometry (DGfZ, 2002). Besides his interests in fine arts and travelling, he is co-founder of BioContact e.V., co-organizer of the Contact-2001, -2002 and -2003 life-science industry fairs, as well as a member of The American Association for the Advancement of Science (AAAS), the Foresight Institute, the Bund für Umwelt und Naturschutz Deutschland (BUND), the German Society for Human Ecology (DGH), and the Human Ecology group at the Ruperto-Carola University, Heidelberg.