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Dissecting the biogenesis of eukaryotic ribosomal subunits

Objective

In all living cells, the important task of protein synthesis is carried out by the ribosome. A substantial amount of cellular energy and resources is utilized to manufacture ribosomal subunits. In contrast to prokaryotes, eukaryotic ribosome assembly requires a multitude of conserved non-ribosomal trans-acting factors, which transiently associate with pre-ribosomal particles at distinct assembly stages and perform specific maturation steps.
Large-scale proteomic approaches in budding yeast, have rapidly expanded the inventory of trans-acting factors (~200). However, little is known regarding their precise site(s) of action and the role(s) of these factors during pre-ribosome assembly. Upon accomplishing their task, majority of the trans-acting factors, are typically released from maturing pre-ribosomes already in the nucleolus/nucleus. Strikingly, a handful of factors remain associated with pre-ribosomes and facilitate their export into the cytoplasm. Release of these factors constitutes “late cytoplasmic maturation events” which render exported pre-ribosomes translation competent. In this proposal we will exploit the powerful model organism budding yeast to:
(1) Develop novel biochemical tools to elucidate the molecular environment of trans-acting factors on the surface of pre-ribosomal particles. These analyses will provide us a low-resolution biochemical map of a maturing pre-ribosome.
(2) Exploit the powerful combination of genetic and high-throughput visual screening approaches in budding yeast to unravel novel “late cytoplasmic maturation steps” in the 60S biogenesis pathway.

Together, my research proposal aims to contribute significantly to our current knowledge regarding the construction and nuclear export of eukaryotic pre-ribosomes. Our analysis will lead us to general principles that underlie the dynamic assembly/dissassembly of large macromolecular ribonucleo-protein complexes.

Field of science

  • /natural sciences/physical sciences/theoretical physics/particles

Call for proposal

ERC-2010-StG_20091118
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Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Address
Raemistrasse 101
8092 Zuerich
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 500 000
Principal investigator
Vikram Govind Panse (Prof.)
Administrative Contact
Vikram Govind Panse (Prof.)

Beneficiaries (1)

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Switzerland
EU contribution
€ 1 500 000
Address
Raemistrasse 101
8092 Zuerich
Activity type
Higher or Secondary Education Establishments
Principal investigator
Vikram Govind Panse (Prof.)
Administrative Contact
Vikram Govind Panse (Prof.)