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).

Poly(A) 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 poly(A) tail length can be used to fine-tune protein synthesis, for example during development. Although the proteins that add and remove poly(A) 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 poly(A) tails on mRNAs. We aim to understand how these complexes are regulated, how they recognise mRNA, and the specific roles of subunits.

I am looking for a motivated and enthusiastic student to join the group.  A wide range of techniques are employed by the group, including cryo-electron microscopy (cryo-EM), x-ray crystallography, genetics, biophysics and biochemical assays.

Please see my website for more information.

References:

Stowell JA, Webster MW, Kögel A, Wolf J, Shelley K, Passmore LA (2016)
Reconstitution of Targeted Deadenylation by the Ccr4-Not Complex and the YTH Domain Protein Mmi1
Cell Reports 17(8):1978-1989.

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.
EMBOJ 33(14):1514-26.

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.
Science 346:1377-1380.