Research objectives and content
Gene expression is regulated through transcriptional control, RNA processing, transport and localization rf RNA and translational control. A central element in this control system is the pre-mRNA splicing reaction mediated by a large RNA-protein complex called spliceosome.
The aim of my PhD project will be to gain a more detailed insight into the structural organisation of snRNPs in order to understand the catalytic mechanism of pre-mRNA splicing at a molecular level. The project will be focused on U2 snRNP which is involved in branch site recognition. I will reassemble the U2 12S snRNP particle and parts thereof from overexpressed protein subunits and different RNA constructs for the biochemical characterisation and crystallographic analyses. The project is concerned with specific protein-protein and protein-RNA interactions within snRNPs, about how snRNPs achieve specific recognition of short RNA sequences within pre-mRNA and about interactions within snRNPs upon assembly into the entire spliceosome. Besides the information about this important biological process, general ideas about protein-protein and protein-RNA interaction are expected to evolve.
Training content (objective, benefit and expected impact)
The project offers a wide variety of different techniques ranging from molecular biolgy and protein biochemistry to structure determination, especially a profound training in xray crystallography. It also provides a deep theoretical knowledge about protein and RNA structures.