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Biophysical Genomics

Investigating the complex sequential and three-dimensional organization of genomes.

Group Leader
Dr. rer. nat. Tobias A. Knoch
Group Members
Michael Lesnussa (programmer), Martijn Muetgeert (programmer), Anis Abuseiris (student), Rob de Graaf (student), Erwin Hoeckx (student), Remko Kleinjan (student), Arjen Lammers (student), Redemar van Leeuwaarden (student), Niels Naglé (student), Ricardo F. Peters (student), Kishan Shri (student), Sander van Vliet (student)
[group members are also members of the GLOBE-Consortium]

Abstract
The enormous system-biological complexity of genome organization, i.e. their general sequential, three-dimensional and regulatory architecture still remains largely unclear despite the immense scientific achievements so far. We investigate this complex organization of genomes from the DNA sequence level to the morphology of entire cell nuclei by theoretical and experimental biophysical means. We also founded with Hubert J. Eussen (Dep. Clinical Genetics, Erasmus MC) and Michael J. Moorhouse (Dep. Virology, Erasmus MC) the interdisciplinary and interdepartmental GLOBE-Consortium. Here we have recently developed the next-generation “ GLOBE 3D Genome Viewer” and we currently set-up together with Luc the Zeeuw from the Hogeschool Rotterdam, the “ Erasmus Computing Grid” one of the largest desktop computing grids in the world.


Introduction
Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional and regulatory organization.

We investigate this complex organization of genomes from the DNA sequence level to the morphology of entire cell nuclei by theoretical and experimental means combining molecular biology in highly interdisciplinary projects ranging from advanced sequence analyses of genomes, parallel high-performance computer modeling of genomic architectures and new image analysis methods, to advanced fluorescence in situ hybridization labeling and high-resolution chromatin conformation interaction genome mapping. A major achievement was also the development of a now widely used artefact-free in vivo labeling method of nuclear chromatin.

Beyond we founded together with Hubert J. Eussen (Dep. Clinical Genetics, Erasmus MC) and Michael J. Moorhouse (Dep. Virology, Erasmus MC) the interdisciplinary and interdepartmental GLOBE-Consortium where we develop together an infra-structural basis for genome research: To satisfy the high-performance computing needs of the Erasmus MC and ourselves, we currently build up the Erasmus Computing Grid (ECG) together with Luc de Zeeuw and the Hogeschool of Rotterdam. With at the moment ~8000 and a projected ~25000 virtual CPUs, the ECG is one of the largest desktop grids world-wide. We have also developed the GLOBE 3D Genome Viewer, a novel system-biology oriented genome browser necessary to access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning.

Jobs
The group Biophysical Genomics and the GLOBE-Consortium have always open positions for thesis projects and internships on various levels, e.g. HBO student, bachelor and master level.

Please, contact Dr. Tobias A. Knoch, t.a.knoch@erasmusmc.nl