Previous and current research

We are intrigued by the fascinating biochemistry and genetics of the serpins (serine protease inhibitors), a family of proteins with unusual structural and functional diversity. Members of the serpin family cover a remarkably broad spectrum of functions such as protease inhibition, assistance in protein folding, and chromatin condensation, often involving large-scale conformational changes of the molecule fold.

We have identified and characterised serpins that are potent inhibitors of proprotein convertases (PCs), a class of processing enzymes responsible for maturation of hormones, neuropeptides and other cellular proteins. PCs are also involved in far-spread pathologies such as cancer, arteriosclerosis and dementia. In addition, these enzymes are associated with the propagation of many pathogens like HIV, Bacillus anthracis or Ebola virus.

A special interest of our research relates to serpins from Drosophila melanogaster, a small animal that has often proven to be a front runner for solving important biological questions.

Current projects

Serpins: Security guards of the secretory pathway in eukaryotic cells
The secretory pathway represents the major export/import highway for proteins. We are investigating the role of serpins as antiproteolytic security guards along the cellular export/import routes.
Evolution of eukaryotic serpin genes
In contrast to most other eukaryotic protein families, where the exon/intron pattern of their genes has been maintained for hundreds of millions of years, serpin genes display highly divergent gene architectures. We use changes of the exon-intron patterns and other rare genomic characters to resolve the family history of eukaryotic serpins and to study the evolution of serpin genes.
Functional diversification of serpin genes
By mutual exclusive exon splicing, transcription of serpin genes in insects and other animal taxons may generate multiple protease inhibitors from a single gene, able to inhibit a broad spectrum of proteases with different substrate specificity and cleavage biochemistry. Our goal is to unravel the molecular basis enabling generation of these multitasking serpins.
Last update: 11/2010
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