PhD Research Project

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Structural Studies of proteins involved in ribosome biogenesis

Institution:

University of Edinburgh

Dept/School/Faculty:

Cell and Molecular Biology

PhD Supervisor:

Dr A Cook

Application Deadline:

No more applications being accepted

Funding Availability:

Funded PhD Project (European/UK Students Only)

PhD Research Project

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The production of ribosomes in eukaryotes is a highly complex process involving several sub-cellular compartments and more than 200 associated ribosome biogenesis factors. The process starts in the nucleolus where the mature 18S, 5.8S and 25S ribosomal RNAs are transcribed as a single transcript and immediately associate with both ribosomal proteins and assembly factors. The pre-40S and pre-60s ribosomal particles are separated relatively early in assembly and follow different assembly pathways. They are each exported to the cytoplasm where the final maturation steps occur. This process is currently best understood in budding yeast. Biochemical analysis of yeast and human pre-40S particles has shown that the same set of 7 late-acting biogenesis factors is exported with the pre-40S particle in both organisms, indicating that this process is highly conserved. Although we now have an inventory of ribosome biogenesis factors, the function of many of the proteins involved and the mechanism of their action in ribosome biogenesis is unknown. This project will involve the crystallization and structural analysis of proteins involved in late pre-40S ribosome maturation and their complexes with rRNA fragments. The structural studies will be used to design mutants that can be tested in vivo to gain a better mechanistic understanding of the role of these proteins.

Funding Notes:

If you are an overseas student, you should only apply if you have identified a source of funding.

References:

Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2. Zemp et al (2009) J. Cell Biology 185:1167-80

Cracking pre-40S ribosomal subunit structure by systematic analyses of RNA-protein cross-linking. Granneman et al (2010) EMBO J. 29:2026-36

Protein-protein interactions within late pre-40S ribosomes. Campbell and Karbstein (2011) PLoS One. 6:e16194