PHD POSITION IN THE BERGLER LAB
Standort: Graz
Art: Vollzeit
Firma: Institute of Molecular Biosciences, Karl Franzens Univ. Graz
Eingetragen am: 2020-01-23
Kontakt:
Beschreibung:

PhD Position in the Bergler Lab available Institute of Molecular Biosciences
Karl-Franzens University Graz

We are looking for a highly motivated candidate for a PhD position in frame of the 3-year FWF project “Substrate processing by the AAA-ATPase Drg1” starting from January 2020!

Research interests of our lab: The formation of ribosomes in eukaryotic cells is a fascinating
pathway that requires the coordinated manufacture and assembly of about 80 ribosomal proteins with four different rRNAs. The production of several millions of ribosomes represents a major energy consuming activity in each cell and is tightly coordinated with cell cycle progression and proliferation. Therefore, ribosome biogenesis is of especial importance for rapidly dividing cells like tumor cells and is currently regarded as one of the most promising targets for anti-cancer chemotherapy. Our lab is a leading address to study inhibitors targeting ribosome biogenesis and to unravel the kinetics and dynamics of the formation of ribosomes. Further major areas of interest in our lab are the molecular mechanism of nuclear export and the coordination of cytoplasmic and nuclear maturation steps of pre-ribosomes. A key player in this coordination is the AAA-ATPase Drg1, which initiates cytoplasmic maturation of the large ribosomal subunit by releasing shuttling proteins from the precursor particles after export.

Available Project: A current project addresses the function of the human orthologue of Drg1,
the SPATA5 protein. Recessive mutations in SPATA5 have been recently linked to developmental delay, mental disorders, hearing loss, epilepsy and a microcephaly phenotype. Up to now, nothing is known about the molecular basis of these SPATA5-associated disorders. Therefore, the project aims to understand how pathogenic amino acid exchanges in SPATA5 affect the functionality of the protein at the molecular level. The experiments will include CRISPR/Cas9 guided construction of human cell lines carrying selected SPATA5 mutations in tight collaboration with Emilio Casanova (LBI für Krebsforschung, Vienna). The constructed cell lines will be assessed for the impact of the mutations on human ribosome biogenesis. These in vivo data will be complemented by a biochemical and possibly structural characterization of the mutant SPATA5 variants in vitro. Together, these data will provide a basis to understand the detrimental effects of SPATA5 mutations and open up potential directions for medical intervention.

If you hold a Master in life science and you always were curious to understand how proteins function we would be happy to welcome you as a PhD student. Experience with human cell culture would be an advantage! Inquiries to helmut.bergler@uni-graz.at

 

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