"Cell Envelope Elongation in Gram Negative Bacteria."

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

This PhD project aims to increase knowledge of a complex of proteins found in Gram-Negative bacteria responsible for cell elongation and rod shape, known as the elongasome. This complex is primarily responsible for the biosynthesis of an extracellular polymer called peptidoglycan that provides strength, rigidity and shape to all bacterial cells. Previously we have thought of these cellular structures in isolation, but the peptidoglycan polymer is found between the bacteria inner and outer membranes and it's biosynthesis must be coordinated with the formation of these structures as well. In this project we will explore the connection and coordination of peptidoglycan biosynthesis with phospholipid balance systems of Gram-Negative bacteria, to understand the biological function of these complexes in the context of overall cell envelope elongation. The expansion of these topics hopes to contribute to a coherent theory for membrane-peptidoglycan synthesis regulation during cell growth.
This PhD aims to expand the knowledge of both systems in the context of in vivo cell envelopes, to see how these systems might interact and enable the cell envelope to grow without membrane disruption or disorganisation, caused by disfunction of membrane-peptidoglycan growth synchronisation.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
2097310 Studentship BB/M01116X/1 01/10/2018 30/09/2022 Christopher Graham
 
Description A review paper has been finished, and is in the process of publication- on the peptidoglycan network of interactions

A paper on Waal Ligase and its relation to RodAPBP2 was realised thanks to co-evolution.

The mechanism of action for RodAPBP2 is now understood by the team, pending writing and publication

A new assay for Lytic transglycosylase activity has been produced.
Exploitation Route I will continue
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Maintaining cell wall integrity in Gram-Negative Bacteria
Amount £11,645 (GBP)
Funding ID NE/T014717/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 04/2020 
End 03/2021
 
Description Filippo Mancia Cryo-Electron Microscopy Lab 
Organisation Columbia University
Country United States 
Sector Academic/University 
PI Contribution Mutants, and activity testing of RodA-PBP2, structural realisation of RodAPBP2. Theoretical and project guidance on Waal Nature paper. Theoretical and project guidance of RodA-PBP2 paper
Collaborator Contribution Cryo-electron structure of Waal.
Impact A paper on Waal the O antigen Ligase
Start Year 2019
 
Description Outer membrane protein Pseudomonas fluorescence Lori Burrows 
Organisation McMaster University
Department Department of Biochemistry and Biomedical Sciences
Country Canada 
Sector Academic/University 
PI Contribution Creating new theory on outer membrane peptidoglycan interaction, created 6 incredibly intricate vectors for fluorescent visualisation in pseudomonas. Applied to and achieved grant
Collaborator Contribution Visualisation of fluorescence, and pseudomonas knowledge.
Impact New Grant, new research field.
Start Year 2020