Interdisciplinary Centre for Bioinformatics (IZBI)

General

The Interdisciplinary Centre for Bio-Computer Science (IZBI) is an institutional centre of the Universität Leipzig, for which the infrastructure is financed proportionately by third-party grants and internal budget means. The Centre works within its own framework and has at its disposal a scientific staff and administration.

The IZBI is managed by a five-man management board of representatives from the Faculties of Mathematics and Computer Science, the Faculties of Bio-Sciences, the Medical Faculty and the Leipzig Max-Planck-Institute. Prof. Markus Löffler is the Scientific Director of the IZBI.

Research content of the Centre is orientated to the strategic research profile of the Universität Leipzig and help to shape it. The IZBI is involved in four of the six research emphasis-targets of the University.

• Modelling of Biological Processes, Regenerative Medicine: The modelling of Life-Processes under system-biological aspects has become a strategy that is increasing in significance, in order to understand their manner of functioning, to plan experiments and also to guide bio-technological processes. This latter application has special significance in Regenerative Medicine, for example with the conditioning of bio-reactors for the generation of tissue. Mechanisms and processes of gene regulation are modelled as well as the intra-cellular signal processing, cell differentiation and self-organization of tissues.
• Computational Microscopy: Currently a technological revolution is occurring in high-definition in-vitro microscopy with a multitude of technologies (ultra-sound-, infra-red-, in-vivo electron-microscopy, fluorescent microscopy with special labelling and staining techniques), which enable examinations with cellular and molecular definition. It will then be possible to obtain, for a tissue sample, various image modalities with complementary informational content. The comparative analysis of data places huge demands on the image processing and on further informational methods of comparison with findings from molecular diagnostics (see next point).
• Molecular Medicine/Computational Diagnostics: Molecular characterization and demarcation of disease-identities by means of analysis of genomic, proteomic, genetic-impression chemical data and immuno-histo chemical data have been rising considerably in significance. The data attained by several partners, as a rule, in the context of large research associations require management and a concerted effort in assessment, for which the IZBI develops suitable technological platforms (data bases with integrated analysis programmes and analysis algorithms) and makes them available. The high-dimensional structure of the data requires application of qualified statistical data-mining procedures, which can adequately form an image of the biological problem (e.g. for genomic regulation (see next point).
• Interactomics and non-encoded RNA: During the regulation of gene activity in the cell, a multitude of processes interplays in a net-like (reticulated) fashion. Interactions between various molecular components (proteins, RNA, DNA, etc) play a decisive role in this context. Explanation of the working mechanism is a central key to understanding the cell function. It is becoming increasingly clear that, in addition to the (protein)-encoded genes, a considerable part of the genome is attributed to so-called non-encoded RNA. This has, in detail, an extensively unknown, but potentially huge meaning for gene regulation. The possible and previously proved function (in part), of disease processes makes extreme effort in the disclosure of the role of non-encoded RNA necessary. Modern micro-array technologies allow, on the one hand, high-throughput examinations of the aforementioned questions being posed, but also represent (due to a series of unanswered questions) a substantial methodological challenge. The activities of this emphasis-target are therefore also aimed at the development of adequate analysis methods for micro-arrays of the most recent generation (tiling arrays, SNP-arrays, Exon-arrays).

Under methodological reference points, the following emphases have been established at the IZBI:

• Comparative sequence analyses for the identification of specific functional sections of the genome.
• Computer-science-analysis methods for microscopic imaging procedures.
• In-silico simulation and mathematical modelling of cell-differentiation formation and tissue formation in time and space.
• Multivariate statistics and deterministic models for analysis of high-dimensional molecular-biological data.
• Warehousing, integration and documentation of biological and medical data.

The IZBI cooperates with the Professorship, chaired by Prof. Stadler, for Bioinformatics (Department of Mathematics and Computer Science). IZBI and the chair for Bioinformatics together form the Bioinformatics-Initiative funded by the German Research Community (DFG) until 2006.

Results 2006

(1) A core team at the IZBI will be internally financed for 3 more years, in a decision made by the academic senate, after expiration of the DFG financing. The basis for the decision is the fulfilment of a closed target-agreement, which purported research funded by grants from at least eight scientific posts.

(2) In cooperation with the IMISE, the IZBI, with its module “Ontological Tools” (leader Prof. Rahm), is participating in the BMBF-sponsored inter-operational project MEDIGRID. It is the goal of the interoperation to develop and to apply GRID services in bio-medical research. Among other things, highly complex data with use of the resources of networked computational technology are evaluated and interpreted. Ontologies, i.e. negotiated and confirmed vocabulary, are an important prerequisite for the exchange of knowledge. Furthermore, the project develops methods which are made available through the data-processing interoperation.

(3) In two of the projects sponsored by the German Cancer Aid (Deutsche Krebshilfe), molecular causes for cancer diseases (malignant lymphoma and neuroglioma) are examined (project leaders: Prof. M. Löffler, Prof. Rahm). In this interdisciplinary effort, the IZBI assumes bio-informatics analyses of gene expression data and matrix-CGH data, as well as the construction and maintenance of a data-base, in which the cooperation-partners deposit, analyze and exchange histological and molecular findings.

(4) In 2006 the BMBF project MSCartPro (Monitoring and Steering of Cartilage Production) was started with a total of 1.6m Euro sponsorship over 3 years, with central coordination from the IZBI (Prof. Löffler, Dr. Galle). It is the goal of this project to develop a bio-reactor which could enable reasonably-priced and automatic production of articular cartilage replacement tissue from stem-cells of the respective patients. Research groups cooperate here from the Biotechnological-Biomedical Centre (BBZ, Prof. Bader, reactors for the growth of tissues), physics (Prof. Käs, cell-elasticity measurements; Prof. Grill, ultra-sound microscopy) and bio-physics (Dr. Schiller, MALDI-TOF analytics). Single-cell based computer models are being developed at IZBI, which should systematically examine the factors relevant for tissue formation and thereby provide the prerequisites for targeted steering of cartilage regeneration.

(5) Together with Prof. Hengstler (pharmacy), the IZBI is involved in the BMBF project HepatoSys (Dr. Drasdo). Questions concerning liver regeneration are processed under system-biological key points. Tissue models of liver are developed at IZBI.

(6) The topic of “Gene expression analysis“ combines several research groups from the Universität Leipzig with the IZBI. Statistical procedures and evaluation strategies are developed together with the INISE (Prof. Löffler and staff) und the IKIT (Prof. Horn). The IZBI oversees together with the Core-Unit the DNA technologies of the IZKF (PD Dr. Krohn) GeneChip-studies in the context of the East German Reference Centre for Micro-Array Technology.

(7) In cooperation with the IKIT (Prof. Horn), a project was initiated for the target-gene orientated analysis of regulatory gene-sets on gene expression arrays in oncology, which is being funded for two years at IZKF.

(8) The topic “Computational Microscopy“ has developed quite successfully. Dr. Braumann took over the management of the Core Unit “Computational Microscopy“ at the Translation Centre for Regenerative Medicine, which continues to be located at the IZBI.

(9) With the combination of the Institute of Zoology (Prof. Schlegel) and the Institute of Computer Science (Prof. Middendorf), there exists a close collaboration on the topic of pedigree reconstruction and population genetics in complex biological systems. Nine partners are taking part in the European-wide interoperation project, funded by the EU, “Emergent organisation in complex biomolecular systems (EMBIO)“. The organizational principles of complex biological systems are being researched in this undertaking (project managers Prof. Dr. P. Stadler, Prof. Dr. M. Middendorf, Prof. M. Schlegel).

(10) 15 publications and 6 book contributions from the IZBI appeared in internationally recognized journals in 2006.