IZBI is an institutional centre at the Universität Leipzig with its own facilities, team of scientists and researchers, and administration. Its infrastructure is financed through the university budget as well as external funding.
Bioinformatics is an essential component of modern biological and medical research. IZBI successfully established a bioinformatical research profile at the university. The centre concentrates on two major research areas:
1. In the field of Genetic Evolution, it pursues projects analysing genetic diversity and its underlying evolutionary relationships among species.
2. In the field of Tissue Formation and Signal Transduction, IZBI examines the genotype-phenotype dependency in tissue formation and function, with a special focus on the mechanisms of spatial formation of tissue, the architecture of signal transduction and genetic regulatory networks, and the analysis of high-dimensional genomic and molecular data from normal and diseased tissues.
Research at the centre is both oriented with regard to the strategic research profile of the Universität Leipzig and helps organise this profile. IZBI contributes to four of the university's six research concentrations. Bioinformatics at Universität Leipzig focuses on the following topics:
- Modelling of Biological Processes, Regenerative Medicine: A dynamic systems-biology modelling of life processes is an increasingly important strategy to understand their functioning, to plan experiments, and also to guide biotechnological processes. The latter application is especially important in the field of regenerative medicine, for example in the conditioning of bioreactors for tissue engineering. Mechanisms and processes of gene regulation as well as cellular signal transduction, cellular differentiation, and the self-organisation of tissue are being modelled.
- Computational Microscopy: We are in the midst of a technological revolution in the area of high-resolution in-vitro microscopy with a large variety of techniques (ultrasound, infrared, in-vivo electron microscopy, fluorescence microscopy with special labelling and dyeing techniques) which allow analyses with cellular and microscopic resolution, making it possible to secure different image modalities with complementary information from a tissue sample. The comparative analysis of those data makes high demands on image processing and further computational methods, compared to findings in molecular diagnostics (see next item).
- Molecular Medicine/Computational Diagnostics: The molecular characterisation and differentiation of disease identities through the analysis of genomic, proteonomic, gene expression, and immunohistochemical data is rapidly growing in importance. Those data, typically collected by several partners within the framework of large research collaborations, requires management and concerted evaluation, for which IZBI is developing and offering adequate technological platforms (databases with integrated analysis programmes and algorithms). The high dimensional structure of those data requires the application of qualified statistical data mining processes, capable of adequately representing the biological problem, for example genomic regulation (see next item).
- Genomic Regulation Networks and non-coding RNA: In regulating the gene activity of a cell, a multitude of processes form interlinked networks. Understanding mechanisms and topology of those regulatory networks is a key to understanding cell function. It is becoming increasingly evident that, in addition to the (protein) coding genes, a significant part of the genome has to be assigned to non-coding RNA. This plays a largely unknown, but potentially very important role in gene regulation. Its probable and partially substantiated function in disease processes requires a special effort to uncover the role of non-coding RNA.
IZBI maintains close ties to the Chair for Bioinformatics (Prof. Stadler) at the Faculty of Mathematics and Computer Science. IZBI and the Chair for Bioinformatics together form the Bioinformatics-Initiative, funded until 2006 by the National Research Foundation DFG.
Research Organisation and Concept
Research at IZBI is organised in four Working Groups and one Junior Research Group with the following emphases:
Working Group 1: Databases and Data Integration for Bioinformatic Tasks (coordinator: Prof. Dr. E. Rahm). The Group focuses on the management, integration, annotation and ontology of molecular-biological and genetic data. In close cooperation with Working Group 3, a data warehouse for gene expression analysis (integration, annotation and analysis of large amounts of genomic and transcriptional information) was developed. It is being used as a platform for data management and analysis by a number of research projects in the areas of cell biology and medicine, as well as by two large national collaborative projects funded by Deutsche Krebshilfe (German Cancer Aid Society), which aim to understand the molecular causes of malign diseases,.
Working Group 2: Tissue Organisation, Cell Differentiation and Computational Microscopy (coordinator: Prof. Dr. M. Löffler, Dr. D. Drasdo). The Group's research concentrates on single-cell based simulation models of tissue organisation and cell differentiation (e.g. tumours and epithelia) and connected methods of "computational microscopy" imaging techniques, like e.g. 3D-reconstruction of serial sections. The Group cooperates closely with a number of research groups in the Faculty of Medicine and the Centre for Biotechnology and Biomedicine BBZ in questions related to cell growth and cell migration in regenerative and carcinogenic tissue. This year, members of the Group were awarded two research awards for the medical application of computational imaging techniques (see below).
Working Group 3: Cellular Signal Transduction and Gene Expression (coordinator: Prof. Dr. F. Horn). The Group concentrates its research on questions of functional genomics in the context of pathogen processes with the particular application of gene expression analysis through microarrays. Its methodical emphasis is on the development of statistical and model-based algorithms for the analysis of gene expression and matrix-CGH data. Together with the Core Unit "DNA-Technologies" at the Interdisciplinary Centre for Clinical Research IZKF, the Group advises users of expression arrays in the analysis and interpretation of gene expression data. The Group closely collaborates with Working Group 1 on warehouse applications. The Group is also partner in two collaborative medical projects funded by Deutsche Krebshilfe (German Cancer Aid Society).
Working Group 4: Genetic Evolution (coordinator: Prof. Dr. P. Stadler). The Group analyses gene and protein sequences with a special focus on population genetics and phylogenetics, e.g. for the purpose of phylogenic tree reconstruction or for the purpose of identifying non-coding RNA.
Junior Research Group: Multicellular Systems (coordinator: Dr. D. Drasdo). This group is part of Working Group 2, and focuses on computer models for spatial and temporal tissue formation and organisation with a special focus on complex regulatory mechanisms.
Results 2005
1. Cooperation between IZBI and partners within Universität Leipzig and beyond was significantly increased both with regard to the number of topics, and in terms of the number of partners. This development is based on IZBI's competency and the resulting demand of bioinformatic services. IZBI was very actively involved in central project initiatives (i.e. RegMed). It also initiated several collaborative projects and organised their scientific coordination.
2. In 2005, IZBI produced 20 publications in international refereed journals and 3 book contributions.
3. Together with the Institute of Medical Informatics, Statistics and Epidemiology IMISE, IZBI takes part in the collaborative project MEDIGRID, partially funded by the Federal Ministry of Education and Research. Over a period of three years, IZBI receives EUR 154,000. MEDIGRID aims to prove the applicability and relevance of GRID-services in medicine and the life sciences, using the example of biomedical research with high dimensional data and the correlative connection of a large variety of genotypical and phenotypical data.
4. Two projects supported by the Deutsche Krebshilfe (German Cancer Aid Society) research the molecular causes of cancer (malign lymphoma and glioma). Project coordinators are Prof. Dr. M. Löffler and Prof. Dr. E. Rahm. In those interdisciplinary projects, IZBI is responsible for bioinformatic analyses of gene expression and matrix-CGH data, and for designing and maintaining a database where cooperation partners can store, analyse, and exchange histological and molecular results.
5. Cooperation with research groups from the Centre for Biotechnology and Biomedicine BBZ was intensified. Projects in cell biology, i.e. concerning the growth of cartilage tissue in bioreactors (Prof. Dr. A. Bader) or cell adhesion and tissue formation (Prof. Dr. A. Robitzki) were initiated. Further partners are: Prof. Dr. J. A. Käs/Dr. J. Guck (Physics, cell elasticity measurement techniques), Prof. W. Grill (Physics, ultrasound microscopy), Prof. K. Arnold/Dr. A. Schiller (Biophysics, MALDI-TOF Analysis), Prof. J. C. Simon (Dermatology Clinic, stem cell cultures). A close cooperation concerning questions of cell biology exists with the group of Prof. Dr. G. Aust (Centre for Surgery) in the area of molecular oncology and with Prof. Dr. J. G. Hengstler (Pharmacy) concerning questions of liver regeneration. The expertise contributed by IZBI concerning the modelling of tissue growth is complemented by partners from the Institute of Medical Informatics, Statistics and Epidemiology IMISE (Prof. Dr. M. Löffler, Dr. I. Röder) with their expertise in stem cell models.
6. "Computational Microscopy" has developed very successfully. At its centre is the intensive cooperation with the Department of Obstetrics and Gynaecology (Prof. Dr. M. Höckel, Dr. J. Einenkel) and the Institute for Pathology (Prof. Dr. F. Horn), which succeeded in a three-dimensional imaging of fine structures of cervical carcinoma with cellular resolution. In connection with the RegMed-Initiative, several research groups from Universität Leipzig were brought together with groups from the universities in Halle and Dresden, each providing unique microscopy techniques for biomedical applications. Optical procedures (infrared and Raman spectroscopy imaging) and cytometric methods (Heart Centre Leipzig) are complemented by ultrasound (Universität Halle and the Faculty of Physics and Earth Science Universität Leipzig) and in-vivo electron microscopy (Max-Planck-Institute of Microstructure Physics Halle). IZBI is planning to develop a "microscopy server," which will bring together the different methods and help realize morphometric analyses.
7. The IZBI working group for Computational Microscopy, together with its partners from the Department of Obstetrics and Gynaecology (Prof. Dr. M. Höckel, Dr. J. Einenkel) and the Institute for Pathology (Prof. L. Ch. Horn), was awarded two renowned science awards:
- The annual award by the "Deutsche Gesellschaft für Ultraschall in der Medizin DEGUM" was given to a work on the sonomorphological topography of the female pelvis, which successfully established a standardisation of the ultrasound examination procedure.
- The "Varian Award for Radiotherapy" was awarded by the Swiss Society of Radiobiology and Medical Physics SGSMP for a new microscopic image processing sequence for the three-dimensional reconstruction and morphometrical quantification of the tumour invasion front in cervical carcinoma, using large histological serial sections. The awarding committee concluded that the work is of pre-eminent importance for clinical research, especially if this method can be successfully applied to other tumours. This would in turn make it possible to determine probabilities for the spreading of tumours and to develop prognostic factors.
8. "Gene Expression Analysis" connects several research groups of the Universität Leipzig with IZBI. Statistical analyses and strategies for evaluation are being developed in cooperation with the Institute of Medical Informatics, Statistics and Epidemiology IMISE (Prof. Dr. M. Löffler and colleagues) and the Institute of Clinical Immunology and Transfusion Medicine IKIT (Prof. Dr. L. Chr. Horn). Within the framework of the East German Microarray Technology Centre, IZBI oversees GeneChip studies together with the Core Unit DNA-technologies of the Interdisciplinary Centre for Clinical Research Leipzig IZKF (PD Dr. K. Krohn).
9. There exists a close cooperation with the Institute for Zoology (Prof. Dr. M. Schlegel) and the Institute for Computer Science (Prof. Dr. M. Middendorf) concerning the topic phylogenic tree reconstruction and population genetics in complex biological systems. Nine partners cooperate in the Europe-wide collaborative project "Emergent Organisation in Complex Biomolecular Systems EMBIO," supported by the European Union. This project examines the organisational principles of complex biological systems (project coordinator are Prof. Dr. P. Stadler, Prof. Dr. M. Middendorf, Prof. Dr. M. Schlegel).
10. IZBI initiated, organised, or co-organised the following conferences and workshops:
- The conference "Road to the RNA-World: Intersections of Theory and Experiment," organised by IZBI and the chair for Bioinformatics, June 9-11, 2005.
- The international workshop StemCellMathLab'05 (May 26-28) about concepts and mathematical models of tissue stem cell organisation, organised together with the Institute of Medical Informatics, Statistics and Epidemiology IMISE.
- A workshop about graph theory, also in May 2005, under the leadership of the chair for Bioinformatics and IZBI.
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