The present research report represents an overview on the activities during my final years as Director of the Institute of Medical Virology at the University of Zurich.

I had to undergo mandatory retirement by the end of August in 2008. The final two years were characterized by high research activities of all scientific coworkers in order to finalize experiments for publications, prepare oral presentations for interviews and applications for new positions. More than 20 coworkers left to many different countries, Australia, Russia, Libanon, Pakistan. Many of them were able to find attractive positions within Switzerland. Dr. G. Radziwill obtained an appointment for teaching as University Professor at the University of Freiburg, Germany.
The scientific emphasis during my final year was on understanding the signaling kinase cascade and antagonistic tumor suppressors. The anti-proliferative effects of tumor suppressors with PDZ-domains was the topic of my last SNF-financed project. We characterized several tumor suppressors such as the Bcr Kinase in the Wnt pathway, the junction protein Afadin AF-6, the disc-large(Dlg)-related membrane protein MPP2, the ubiquitin ligase LNX. The c-Raf kinase, discovered in our laboratory, and the oldest known oncogene Src, were shown to be negatively regulated by PDZ proteins. Surprisingly, a single amino acid change at the very C terminus will make Src metastatic (loss of binding to PDZ domain).
We described a novel differentiation marker protein for adipocytes, which may bear relevance for insulin metabolism. We characterized the DNA plasmid-coded IL-12 in combination with other drugs for anti-cancer effects.
Furthermore, new small hairpin-loop-structured DNA oligonucleotides were shown to be an alternative to siRNA and antisense DNA, being able to inhibit virus replication but also inactivate HIV cell-free virus particles, designated as suicide. This is under consideration for drug development, possibly for prevention of sexual transmission of HIV.
During my Directorship I increased the annual budget of the Diagnostics Dept about 15fold in about 10 years (6MioCHF, 50.000 analyses)). This was mainly achieved by introducing novel molecular diagnostics technologies to increase speed and specificity. Furthermore the number of diagnostic analyses was expanded in particular offering analyses for transplant patients of the University Hospital. Tests for Biosafety were developed by molecular techniques and made quickly available, e.g. for pox virus diagnostics.
After my retirement I started a new research laboratory on Viruses and Cancer in a Science and Technopark, Zürich, associated with the University.
I initiated studies at the Max Planck Institute of Molecular Genetics, Berlin, as member of the group of Prof. H. Lehrach, on new scientific projects on endogenous retroviral elements and their role in the human genome.
I was Fellow of the Institute of Advanced Study at Berlin 2008/2009. During that period I started a new topic on retroelements in the human genome and evolution of retroviruses, which I will follow up in the future. I finalized previous work and published more than a dozen papers after retirement. I organized a workshop on Evolution of Viruses and Hosts – my future interest.

Zürich/Berlin, October 2009

Karin Moelling

HIV / RNase H Viruses Oncogenes and Cancer Kinases PDZ Proteins

Gene Silencing

Gene Medicine and Therapy