The structure and function of the ß-barrel assembly machinery


I am a structural biologist with a particular interest in the function of membrane proteins. Having completed my undergraduate degree in biochemistry at the University of York, I decided to pursue a PhD at the University of Leeds to take advantage of their world class cryo-electron microscopy (cryo-EM) facilities and the opportunities these presented for structural work.

The outer-membrane folding problem

Gram-negative bacteria have a unique cell envelope, containing both an inner and an outer-membrane. The integral membrane proteins of the outer-membrane (Outer-membrane proteins or OMPs) are essential for both bacterial survival and virulence, making their biogenesis of potential medical relevance. As OMPs are unable to fold unassisted into the outer-membrane, a protein machine called the ß-barrel assembly machinery (BAM) complex catalyses this process by a currently unknown mechanism.

Understanding the BAM complex

 In my PhD project I will focus on structurally characterising the BAM complex in the different conformations it adopts during function, in order to better understand its mechanism. As the complex is highly dynamic, this will require ‘locking’ BAM in single conformations such that they can be resolved by cryo-EM. This will be accomplished either using BAM mutations known to reduce function, or using inhibitors of the complex, in the hope these work by freezing BAM at one stage of its functional cycle. These efforts will hopefully reveal the range of conformations that BAM adopts during function, as well as potentially allowing structures of BAM bound to stalled substrates to be determined, directly shedding light on the mechanisms by which these substrates are folded.