University of Zurich

Principal Investigator:
Steffen Gay

Main tasks in the project and previous experience relevant to those tasks:

The Center of Experimental Rheumatology at the Department of Rheumatology at the University Hospital will contribute through its expertise in molecular and cellular biology. Epigenetic modifications in rheumatic and cardiovascular diseases including methylation, acetylation, sumoylation and microRNA, represent the major focus of current research. The molecular and cellular basis of joint destruction in rheumatoid arthritis involves especially the search for novel genes and their signaling pathways (“Functional Genomics”). The laboratory explores the processes of synovial adhesion to cartilage and bone, the activation of synovial cells to invade and the cellular interactions with cells of the immune system.

Somatic gene transfer is applied to inhibit synovial cell-mediated cartilage destruction in the SCID mouse model engrafted with normal human cartilage and rheumatoid synovial tissues or isolated cells. Anti-sense constructs, ribozymes , siRNA and antagomirs are used to identify specific targets for future therapeutical interventions. The model is further employed to explore the effect of novel drugs from the pharmaceutical industry.

A new clinical Research Program has been developed entitled “Molecular Analysis of Gene Expression modulated by Novel Drug Therapies” to study the molecular effects of drugs on individual human cells to detect novel modes of action as well as unwanted side effects to develop safer therapeutics.

The center has established a molecular biology training course, twice a year, to train new international research fellows in Serex antibody detection, cloning, sequencing, analysis of methylation, acetylation and miRNAs, cell-culture, cell-sorting (FACS), TaqMan Real Time PCR, primer design, in situ PCR, in situ hybridization and immunohistology.

Short profile of the staff that will carry out the work:

Steffen Gay, MD, M, Director of the Center of Exp. Rheumatology
Renate E Gay, MD, F, Head of Laboratory for Molecular Biology
Astrid Jüngel, PhD, F, Docent and expert in acetylation
Michel Neidhart, PhD, M, Prof and expert in methylation
Caroline Ospelt, MD PhD, F, Senior Post-doc and expert in miRNA
Emmanuel Karouzakis, researcher
Kerstin Klein, researcher
Christoph Rudolf, finances
Alexandra Schneider, admin.
Tiffany Cheok, admin.