Structure and function of macromolecular machines
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Gene expression is tightly controlled to allow rapid responses to cellular stimuli. It is regulated through transcription, translation and mRNA stability. Its deregulation is associated with human diseases (e.g. cancer).
PolyA tails are found on almost all eukaryotic mRNAs. They play important roles in mRNA stability, are required for export of mRNA from the nucleus and regulate the efficiency of translation. Thus, control of polyA tail length can be used to fine-tune protein synthesis, for example during development. Although the proteins that add and remove polyA tails are known, their mechanisms are poorly understood.
We are interested in understanding how macromolecular machines contribute to the regulation of gene expression. Specifically, we are investigating the multi-protein complexes that add or remove polyA tails on mRNAs. We aim to understand how these complexes are regulated, how they recognise mRNA, and the specific roles of some of the subunits.
I am looking for a motivated and enthusiastic student to join the group. A wide range of techniques could be employed (depending on the student’s interests) including cryo-electron microscopy, x-ray crystallography, genetics, biophysics and/or biochemical assays.
Please see my website for more information.
Wolf J, Valkov E, Allen MD, Meineke B, Gordiyenko Y, McLaughlin SH, Olsen TM, Robinson CV, Bycroft M, Stewart M & Passmore LA (2014)
Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation.
Schreieck A, Easter AD, Etzold S, Wiederhold K, Lindschrieber M, Cramer P, Passmore LA (2014).
RNA polymerase II termination involves CTD tyrosine dephosphorylation by CPF subunit Glc7.
Nat. Struct. Mol. Biol. 21: 175–179
Russo CJ, Passmore LA. (2014)
Ultra stable gold substrates for electron cryomicroscopy.