Four year PHD studentship: Open to all UK and EU citizens

Folding and chaperoning outer membrane proteins: Structural biology guided routes towards new antibiotics

 

Gram negative bacteria are surrounded by envelopes with hundreds of proteins that reach this compartment after crossing the cell's membrane and traversing the periplasmic space. Exporting functional proteins to the envelope is an essential, complex process that is poorly understood. It is also an important target for the development of new, and much needed, antibacterial agents. Transport of folding proteins to the outer-membrane (called OMPs) required chaperones and an amazing and currently functionally mysterious complex called the beta-barrel assembly machinery (BAM). Crystal structures of the chaperones and Bam complex are known, but how these proteins all work together to make new, folded and functional periplasmic proteins and successfully folded OMPs in the OM remains undetermined.

 

This 4 year PhD project will use an array of biochemical, biophysical and structural methods to determine how the chaperones SurA, Skp and others, recognise, bind and transport their client OMPs and deliver them to BAM for successful folding into the outer membrane. To achieve this you will learn and employ a variety of methods that could include fluorescence, single molecule methods, NMR and mass spectrometry. These experiments will not only reveal how SurA recognises and binds its substrates, but will allow us to compare how the same clients bind to Skp and SurA with 1000-fold difference in affinity and how all of these proteins function and are coordinated to bring about efficient folding and membrane insertion of OMPS in an environment that is devoid of ATP.

 

The student employed will be part of a consortium that involves five research groups, funded by EOS Belgium. You will join a dynamic team of postdocs and students in the Radford lab who focus on OMP folding and BAM function. The project also brings the opportunity to travel to the laboratories of our collaborators in Belgium to gain new experiences during your PhD. The grant will provide funds for fees, stipend and all research costs.

 

For more information about the Radford group and for recent publications please see http://www.astbury.leeds.ac.uk.

For further details and to apply please go to:

https://www.findaphd.com/search/ProjectDetails.aspx?PJID=92021/