Communicating across the membrane during bacterial cell division

The activities of various processes are co-ordinated during bacterial cell division. For instance, the constriction of the division septum is linked to new cell wall synthesis at the division site, which is necessary to stop the cell from bursting due to turgor. Moreover, the proteins of the contractile ring at the division site are cytosolic, yet the enzymes that perform the final, essential polymerising steps in cell wall biosynthesis are found on the outside face of the plasma membrane. Essential activities thus have to be co-ordinated across the membrane, and there is currently a dearth of information on how this takes place. The formation of the cell wall is essential for bacteria, and this process is the target of antibiotics such as penicillin and vancomycin. While antimicrobial resistance continues to rise, it is pertinent to re-evaulate cell wall synthesis as a target for the generation of novel antibiotics.

We will examine how cell division regulators affect cell wall synthesis, and determine the molecular mechanisms underpinning the regulation. For instance, we are interested in how EzrA, a regulator of septal contraction, is linked to cell wall synthesis. By two hybrid analyses, it is known that EzrA interacts with both PBP1, a key peptidoglycan synthase, and FtsZ, the bacterial homolog of tubulin, which drives septal contraction. EzrA thus links cytokinetic events on the inside of the cell to peptidoglycan synthesis on the outside, but it is not known how EzrA fulfils its communication role. We have recently solved the crystal structure of EzrA, revealing that it resembles the spectrin family of eukaryotic cytoskeletal proteins. We are also interested in how an unrelated cell division regulator, GpsB, appears to co-ordinate the shuttling of peptidoglycan synthases from the lateral walls of the cell during cell growth, to the division site during cytokinesis. We have solved crystal structures of the individual domains of GpsB, and have used SAXS to generate a model of full-length GpsB. We will use the novel structural information and our well-established biochemical procedures to assess the impact of EzrA, GpsB and other regulators (e.g. PBP3, FtsZ, FtsA) on PBP1 function.


The student will focus on trans-membrane communication: how a bacterium co-ordinates processes on both sides of the membrane during division is poorly understood, yet it is essential for the healthy cell. One process that requires such co-ordination, peptidoglycan synthesis, is the target of many overused antibiotics. The strategic importance of the project to the BBSRC is highlighted by the UK government's five year Antimicrobial Resistance Strategy 2013 to 2018. The studentship will underpin the development of novel antimicrobials and alternatives to antimicrobials. The student will receive training in core bioscience skills, and in biochemistry (enzymology) and in biophysics that require rigorous mathematical analysis and understanding of the data (e.g. MST, SPR, ITC, SEC-MALLS), and the student will apply these techniques to the problem of how bacteria build their outer defensive envelopes and how the synthesis of these envelopes is targeted by antimicrobials.