Investigating cell biological aspects of microRNAs-mediated silencing

• Applicant: Professor Dr. Julien Béthune
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 134676348

MicroRNAs (miRNAs) are major regulators of gene expression in a process called silencing. MiRNAs are expressed in animals, and plants. It is estimated that the human genome encodes a thousand of miRNAs regulating about 30% of all protein-coding gene. They were found to be involved in the regulation of virtually all cellular processes studied to date, and changes in their expression is linked to numerous diseases including cancer. Though they have been intensively investigated, it is still unclear how they work and are regulated. Notably, it is currently not known if miRNA-mediated silencing occurs at defined locations within a cell. Moreover, several lines of evidence indicate a possible link between the cytoskeleton and endomembrane dynamics and the miRNA pathway. The cytoskeleton is a dynamic structure that plays important roles in both intracellular transport and cellular division. Endomembranes define specialized intracellular compartments allowing spatial separation necessary to allow certain processes such as protein secretion or modification. The objective of this project is to analyze the cellular organization of miRNA-mediated silencing in order to define where important steps of this pathway are taking place. Moreover, the significance of the cytoskeleton and endomembranes for miRNA-mediated repression will be investigated. To address these issues, novel cell lines will be established that express miRNA-regulated reporters. These reporters, as well as the miRNA-associated machinery will be analyzed by a combination of microscopical, biochemical, and cell biological methods.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Witold Filipowicz