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Coregulation of Pol I, Pol II and Pol III in ribosome biogenesis in mammalian cells


Ribosome biogenesis is tightly linked to cell growth and the coordinated synthesis of the ribosome components involves the three transcriptional machineries.

The networks that control ribosome biogenesis are poorly understood. Data in yeast (C. Carles and M. Riva) suggest that Pol I transcription is the masterchief in the co-regulation of these three machineries for the coordinated synthesis of the ribosome components.

These results rise the following questions and objectives:
- Examine whether co-regulation of the three systems is conserved in mammalian cells.
- Given the important role of ribosomes in cellular growth, investigate whether increased Pol I activation could result in neoplastic transformation.
- Study the mechanisms of the co-regulation.

I will engineer mammalian cells expressing a constitutively active Pol I, based on the yeast approach. I will study the consequences of Pol I deregulation on Pol II and Pol III transcription, ribosome biogenesis and cellular growth that could result in oncogenic transformation.

Relevance to the FP6 objectives:
- Creation of ERA and networks: I will initiate a collaboration between the laboratories of N Hernandez (Switzerland) and C Carles (France);
- Increase the role of women in research: I am a woman;
- Solving major societal questions: our research might provide new clues for anti-cancer strategies.

Relevance to the Marie Curie Intra-European Fellowship objectives, training through research: I will move to the laboratory of N. Hernandez at the CIG (Lausanne, Switzerland) in a competitive institute and learn genome-wide analysis methods. I will benefit from the advice of both N. Hernandez, and C. Carles, with whom I will closely collaborate.

I will meet with renowned scientists both in Lausanne and Paris. I will have the opportunity to manage my own project and to develop it as a group leader in another institute after leaving the University of Lausanne.

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