UBE3A and UBE31 partner protein complexes

This PhD project represents a unique opportunity to combine multi-disciplinary training on leading edge techniques at World class facilities with providing crucially important insight into both the healthy and disease state in an important aspect of human biology. Importantly, the project will provide the student with an appreciation of the value of studying protein-protein interactions on a firm structural, quantitative and functional footing.

UBE3A is an E3 ubiquitin ligase expressed in the human brain whose deficit and incorrect function is associated with several diseases, most notably Angelman syndrome. It also interacts with E6 protein of HPV, as well as being part of larger complexes associated with circardian rhythms.

This PhD project is to understand how UBE3A and its complexes work, and in order to do this we need a detailed picture of UBE3A and its complexes at the molecular level. We will employ protein crystallography and cutting-edge electron microscopy in order to obtain structural and biological information.

The Scott, Layfield and Carr laboratories provide a rich, diverse, supportive and active research environment. The student will be expected to be resident for at least 50-80 % Research Complex at Harwell (www.rc-harwell.ac.uk), where there will be training in protein expression, purification, protein crystallography and electron microscopy. At Nottingham there will be functional pulldown assays in order to assess further binding partners as well as in vitro ubiquitination assays. All facilities are staffed by expert technical staff with post-doctoral qualifications who are available for training and experimental design during the course of this studentship.