EpiGenSys: – Systems biological determination of the epigenomic structure function relation: nucleosomal association changes, intra/inter chromosomal architecture, transcriptional structure relationship, simululations of nucleosomal/chromatin fiber/chromosome architecture and dynamics, and systems biological/medical result integration via the GLOBE 3D genome platform.

Although the sequence of the human genome is known, the relation of its three-dimensional dynamic architecture with its function - the storage and expression of genetic information - remains one of the central unresolved issues of our time. It has become clear that genomes are tremendous co-evolutionary and interwoven molecular storage machines able to manipulate and fabricate information: the genetic information is coded in and along (macro-) molecules that are continually being modified spatially and temporally through a multi-dimensional interaction and regulatory network. Thus, changes in chromatin architecture are central factors in the epigenetic regulation of gene expression and other important genomic processes on length and time scales ranging from 10-9 to 10-5 m and 10-10 to 105 s. Thus, a full understanding of structure-function relationships requires knowledge not only of the linear base-pair composition, but also of its structural and dynamic organization. Therefore, in "EpiGenSys" we have established an unique consortium with the aim of achieving a major breakthrough in the determination and understanding of the relation between DNA sequence, epigenetic modification and spatial chromatin organization. Using truly systems approaches, we studied the following: i) The investigation of nucleosome and chromatin fiber structure and remodelling. ii) The determination of intra/inter chromosomal interactions and chromosomal organization. iii) The analysis of transcriptional states and their relation to the underlying structure. iv) The simulation of nucleosomes, chromatin fibers, and chromosomes to provide theoretical insight. v) The integration of i) to iv) into a systems biological model. We strongly believe that by addressing these fundamental questions using our systems approach to refine our models through reiterative cycling between experiment and theory, we were able to address a central issue of the genomic era - the way structure influences gene activity (and vice versa). Thus, we consider the results achieved to be major breakthroughs in all those above mentioned points. We also anticipate that our results have great impact on wider research communities, and on the development of methods useful for disease diagnosis and treatment e.g. as envisioned by stem cell and gene therapy. This is shown by the number of publications, contributions to conferences and also the still ongoing patenting process. Thus, we think to have made and still make a considerable contribution to systems biology in the genomic sector and in general, as well as contribute to e-Science, e-Health, e-Learning, as well as e-Commerce and increase the awareness and understanding of genomic complexity within society.