Biology and Geography

The Centre for Medical Biotechnology (ZMB) pools the basic biomedical research of over 40 research groups on the campus and at University Hospital. The aim of research at the ZMB is to identify the mechanisms of diseases on a molecular level and to find biotechnological methods that influence these processes and allow the development of new diagnostic procedures and therapies.
The main focus of the Structural and Medicinal Biochemistry department under Prof. Peter Bayer is on the characterisation of parvulin proteins,a class of peptide isomerases which plays an important role in the regulation of the cell cycle and is known to be involved in tumour formation. The researchers were able to identify a new isoform, Par17, which has been discovered to be uniquely present in hominids in the mitochondrial matrix. Structural and functional studies are currently underway – analysis of cell cycle regulation in cooperation with Prof. Kurt Engeland (University of Leipzig).
A second main area of research is the analysis of sulfation processes of proteins which play a crucial functional role for receptors and secreted proteins, e. g. in the infection of cells by HIV or in blood coagulation. The group is investigating the molecular mechanisms of sulfation and the structure of molecules involved in the corresponding enzymatic apparatus. In addition, thescientists are interested in the interaction between HIV and its cellular receptors mediated by sulfa­tyrosines.
In 2007 / 2008, the 700 MHz nuclear magnetic resonance (NMR) spectrometer was the basis for successful cooperation with Dr. Wulf Blankenfeldt (Max Planck Institute Dortmund), Prof. Jutta Eichler (University of Erlangen) and Dr. Igor Zhukov, National Institute of Chemistry, Slovenian NMR Centre, Slovenia.
The Genetics group under Prof. Ann Ehrenhofer-Murray is investigating how genetic material (DNA) is packed into chromatin in the nuc­leus of eukaryotic cells. Differences in chromatin packaging determine where and when specific genes are expressed. In heterochromatin, the DNA regions are silenced; as a result, the genes in these regions are not expressed and the respective proteins are not synthesised, while genes in the less densely packed euchromatin are transcriptionally active. The correct temporal and spatial expression of genes is essential for normal growth and development of the cell.
The latest research findings of the group describe a previously unknown mechanism that restricts the formation of transcriptionally inactive heterochromatin to certain regions of the genome. In another project, the researchers are investigating a histone deacetylase that is associated with the chromatin at the origin of replication. Detailed analyses show which other factors are part of the deacetylase complex, and that itmodulates the initiation of replication by altering chromatin determinants.
The aim of research in Prof. Michael Ehrmann’s Microbiology II group is to understand the molecular mechanisms of protein quality control.It is essential for all organisms to identify defective proteins. The accumulation of defectiveproteins can lead to a loss of essential cellular functions and thereby contribute to the development of diseases such as cancer, Alzheimer’sdisease, Parkinson’s disease or arthritis. Inbacteria, however, the failure of these control mechanisms can compromise the virulence of pathogens.
In the scientific journals Nature and Angewandte Chemie Int. Ed. Engl., the scientists joined with research teams from Vienna (Tim Clausen), London (Helen Saibil) and Dortmund (Markus Kaiser) to describe their latest findings on the multifunctional protein DegP, which eliminates defective proteins, repairs damaged proteinsand protects intact proteins. They found that DegP adapts its own size and activity to the target proteins. The new insights into the functioning of DegP, gained on the atomic level, are seen as potentially helpful in fighting bacterial infections in the future. The development of a new anti­biotic is intended to suppress the bacterial DegP function. In 2009 the group will continue to focus its activities on the evaluation of a crystal structure and the function of the human protease HtrA1, and conduct a high throughput screenfor inhibitors of the stress protease DegS. The aim is to identify better inhibitors and explore their possible implementation as new antibiotics. The role of HtrA1 as a drug target in cancer and Alzheimer’s disease will also be explored.
In March 2008, Prof. Perihan Nalbant took over the Molecular Cell Biology group, and a confocal laser microscope was subsequentlyassembled that can be used to display high-
resolution images of subcellular structures.The group has since conducted its first successful experiments in the generation of three-dimensional images as well as in the dynamic resolution of molecular processes in separate living cells. The goal is to characterise cellular mechanisms which are important for the metastasis of cancer cells. The group therefore intends to focus itsactivities in the coming year on research into regulatory proteins that control the migrationof cancer cells and are therefore critical to the dissemination of the primary tumour.
The research group led by Prof. DanielHoffmann investigates the evolution of bio­molecules using computational methods. Current projects in this field include the development of evolutionary optimisation methods for the automated design of peptides and proteins, and the application of these methods to problems in medical diagnosis. An example of the latter is the design of peptides in the collaborative project “Corus: Co-receptor usage as a marker for specific HIV diagnostics with high sensitivity” (funded by the Federal Ministry of Education and Research, BMBF). Molecules obtained from computational design are tested experimentally in cooperation with other groups, e. g. the Structural and Medicinal Biochemistry group (Prof. Peter Bayer).
The group also applies a wide range ofmethods from biomolecular modelling and bioinformatics to answer specific biomedical questions. One outcome of successful cooperation withthe Institute of Human Genetics of University Hospital Essen (Prof. Bernhard Horsthemke) is the discovery of a mechanistic-molecular explanation of a defect in a zinc finger gene.
The Development Biology team led byProf. Andrea Vortkamp is interested in embryonic differentiation processes of cartilage and bones. During the early stages of embryonicdevelopment, the skeleton of vertebrates is laid out in cartilage before it gradually and successively reaches its final state through the process of ossification. The aim of research in this fieldis to understand genetic or age-related diseases of the skeleton and to develop suitable therapies. The current focus is on examination of two transcription factors, TRPS and Gli3, which regulate the differentiation of chondrocytes and control the size of individual skeletal elements. Patients with mutations of the TRPS1 or Gli3 genes exhibit bone defects and dwarfism, which can be recapitulated and analysed by using a mouse model system. The latest research has shown that an interaction takes place between these two factors. A further focus of interest is the analysis of extracellular signal transduction pathways in thecartilage matrix. The group examined how changes in the sulfation pattern in the extra­cellular matrix affect the process of cartilageand bone differentiation.