Molecular regulation of Antigenetic Variation in protists

• Applicant: Professor Dr. Martin Simon
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2010 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190618734

Unicellular eukaryotes express variable surface proteins via a complicated mechanism which allows them to change their surface structure as if they were simply changing a coat. Parasites use these switching surface coats to escape from the immune system or to identify specific tissues. This is the principle behind chronic infectious disease. Despite its powerful implications and its evolved use in parasites, free-living protists and fungi, the common mechanisms of surface protein expression and switching, are poorly understood. Using the ciliate Paramecium as a model cell in our previous work, we discovered that exclusive antigen expression is controlled by small RNAs in an RNAi like mechanism involving the formation of heterochromatin to silence non expressed antigens. Understanding how genes become silent only begs an additional question: how does a gene escape silencing? Answering this question could lead to a better understanding of how to dispel chronic infections. Our previous work has paved the way to characterize this pathway in detail: analysis of the short RNAs as well as the involved enzymes will clarify the homology dependent effects enabling exclusive expression of surface antigens.

• DFG Programme: Research Grants