Biology and Geography

The Structural and Medical Biochemistry ­research group (Professor Peter Bayer) employs biophysical and spectroscopic methods such as nuclear magnetic resonance to study biomolecular structures and their biological implications. The group is interested in mechanisms and effects of the sulfation of proteins, and the role of cis/trans isomerases in the cell cycle and in chromatin remodelling. Another important topic in the group is the design and structural characterisation of anti-infective mini-proteins (Dr. Anja Matena).
The Genetics research group under Professor Ann Ehrenhofer-Murray examines how genetic material (DNA) is organised in the eukaryote cell nucleus and how alterations in its organisation influence gene transcription. In the course of its work the group has discovered a new mechanism for separating organisational areas from one another in the genome. This is especially important for steering gene activity correctly. Further investigation is concentrating on characterising the relevant proteins and understanding their structure in relation to their function.
The Microbiology II research group of Professor Michael Ehrmann studies evolutionary conserved cellular factors of protein quality control that e. g., recognise misfolded proteins, recover the functional state of these proteins or initiate protein decomposition. Errors in quality control influence cell fate and play a role in bacterial infections, neurodegenerative diseases, arthritis, and cancer, and the research group is investigating this role in several international collaborations. A major subject in recent years has been HtrA, a serin protease involved in quality control. In collaboration with Professor Tim Clausen (IMP, Vienna), the group has been able to uncover structures and mechanisms of HtrA oligomers.
Evolution is the central topic of research in the Bioinformatics group (Professor Daniel Hoffmann) as a key to understanding all biology, including biomedicine. A second unifying aspect of biology is the molecular level at which all biology speaks the same language of genes, proteins, etc. In its research, the Bioinformatics group brings together both fundamental aspects by studying the molecular mechanisms underlying evolution. The group in this way analyses biodiversity in ecosystems based on “deep sequencing” data, or the evolution of human pathogenic viruses such as HIV or HCV under selection pressure by immune systems and antiviral drugs.
The Chemical Biology research group (Professor Markus Kaiser) investigates small molec­ules that specifically interfere with biological processes. Such molecules are interesting tools for basic research and in the development of medical drugs. Starting from bioactive natural compounds, the group designs and synthesises such small molecules and evaluates their biological effects using classical methods and novel chemical proteomics approaches. Promising examples from the last two years include the development of analogues of the proteasome inhibitor Syringolin A (which could be used to develop a drug against leukaemia), the elucidation of the molecular action of the anti-malaria natural compound Symplostatin 4, and the first chemical synthesis of the cytotoxic substance Symplocamide A. Alongside these, the group is also working on the development of the Activity-Based Protein Profiling method for proteome-wide measurement of enzyme activity.
Employing modular cell-based assay systems, the Molecular Biology II research group (Professor Shirley Knauer) seeks to identify novel anti-cancer agents. In an interdisciplinary collaboration
with the Chemical Biology and Bioinformatics groups, specific topics include interference with the nucleo-cytoplasmic transport of the small tumor-protective protein Survivin and inhibition of the oncologically relevant protease Taspase1. Here attempts are made among other things to block the cancer-promoting action of these ­“molecular scissors” with “chemical glues” immobilising the subunits of the protease.
Cells must accurately regulate not only the production of their components but also their decomposition. The Molecular Biology I research group (Professor Hemmo Meyer) is investigating the function of a nano-machine, Cdc48/p97, that plays an important role in the removal of the damaged or aggregated proteins that frequently occur in degenerative diseases and can lead to cell damage. At the same time, Cdc48/p97 helps to degrade regulatory factors and thus inhibits genetic mutations and uncontrolled cell divisions that can contribute to cancer genesis.
The main interest of Professor Perihan Nalbant’s research group is in cellular signal cascades that control the dynamic modulation of the actin-­cytoskeleton. The group works in particular on regulatory proteins that influence cell migration and thus play an important role in pathological processes, e.g. in tumour invasion or in the formation of metastases. The migration of single cells requires the spatio-temporal interplay of dynamic cell protrusions and cellular traction forces. With high-end fluorescence microscopy and RNAi-based manipulation of individual ­proteins, the group has been able in recent years to identify specific signal cascades in invasive ­tumour cells that enable the coupling of such traction forces with dynamic substrate binding, and thereby efficient cell migration.
The Developmental Biology research group of Professor Andrea Vortkamp investigates the molecular causes of genetic and degenerative ­diseases of the skeleton that may lead to malformation, short stature, restricted mobility, pain and tumour growth. Based on the growth factor Indian hedgehog (Ihh), a major regulator of bone formation, the group is concentrating on the transcriptional and epigenetic control of chondrocyte differentiation, especially the interaction of Trps1 and Gli3 with chromatin ­modifying factors. A second focus concerns the question of how the propagation of secreted ­molecules is regulated in the extracellular space. The group is looking at the question of how the structure of extracellular heparan sulphate determines the activity and distribution of Ihh and other growth factors in the surrounding tissues.