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Structural studies of the RNA polymerase II transcription machinery: mechanism of start site selection

Obiettivo

The current application concerns the mechanisms of transcription initiation in eukaryotic cells. The postdoc-project will be carried out in Prof. Roger D. Kornberg's laboratory at Stanford University, California.

THE SPECIFIC AIM of the project is a molecular understanding of how RNA polymerase II (RNAP II) together with the general transcription factors (GTFs) can recognize promoter DNA and initiate RNA synthesis at a specific genomic location.

Reports have shown that RNAP II and TFIIB are solely responsible for this process, but the underlying mechanism is still not known. Recently the structure of a RNAP II/TFIIB cocrystal has been solved in budding yeast. The transcription start site differs however in this yeast compared to fission yeast and most other eukaryotes including human so a general model for the selection process could not be elucidated from this structure.

OUR MAIN OBJECTIVES are to do structural analysis of a RNAP II/TFIIB complex in fission yeast with X-ray crystallography and compare it to t he budding yeast structure. We will complement the structural information with mutational analysis of TFIIB in a pure in vitro transcription system derived from fission yeast developed by me as a Ph.D. student.

THE OVERALL GOAL with the project is to generate a general molecular model for the transcription start site selection process.

My stay will lead to the acquirement of new technological knowledge such as structural analysis of multi-protein complexes with X-ray crystallography that I believe will be a vibrant scientific field in the future.

I will also be able to develop a scientific network that will be useful for my future career as a scientist, as well as the European community, after my return to Sweden.

Invito a presentare proposte

FP6-2002-MOBILITY-6
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Coordinatore

KAROLINSKA INSTITUTET
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Indirizzo
Nobels väg 5
STOCKHOLM
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