UK-BaCWAN2: Continuation and Expansion of UK-Bacterial Cell Wall Assembly Network

Lead Research Organisation: University of Sheffield
Department Name: Molecular Biology and Biotechnology

Abstract

Millions of people die each year from bacterial infections and tens of millions suffer from the consequences of these infections. The discovery of the antibiotic penicillin once opened the door to treat these infections by stopping bacteria making the polymer in the cell wall that holds them together. This polymer, called peptidoglycan, is made up of an interlocking network of sugars and strings of amino acids (peptides). Specialised proteins (called PBPs), with the ability to stitch together these sugars and peptides are the targets inhibited by penicillin, stopping cell wall synthesis and killing the bacterium. Many important bacteria are now no longer killed by penicillin and other antibiotics that attack other stages in the production of peptidoglycan. Bacteria have changed, evading the action of these antibiotics. We need to fight back, by using the advanced computing power at our disposal to design new classes of antibiotics, compounds that will work against multiply resistant bacteria like MRSA, and help combat the harmful effects of our immune system when it over responds to infection.
BACWAN consists of a group of scientists from academia, industry and government whose goals is increase and coordinate activity in his area to bring about new treatments and strategies. They will have, for the first time, the combined tools and new chemical reagents (to be made for the team at a cost efficient central location at Warwick) to look in minute detail how peptidoglycan is made, how we could stop this process by the development of new inhibitors (antibiotics) and how fragments of peptidoglycan interact with our bodies during the process of infection. This capacity for discovery, being lost elsewhere, will provide a unique forum for the development of new compounds.

Technical Summary

The process of assembly of the bacterial cell wall is a validated and important target for the development of novel antibacterial agents, and is intimately connected with the emergence of antibiotic resistance around the world. Significant research programmes in this area are carried out in UK laboratories, but at present these activities are somewhat fragmented, between groups in Chemistry, Physics, and Biology departments following different areas related to this problem. Our existing UK Network in bacterial cell wall assembly, has been successful in bringing together some of these groups with expertise in different disciplines and provide a forum for the additional involvement of industrial and healthcare associated scientists, to inform the network of industrial interests and emerging techniques and areas of interest. We now wish to capitalise and expand upon this network by recruiting further members and promoting excellent scientific collaboration. The principal vehicle for this network will be a series of bi-yearly meetings involving chemists, biochemists, microbiologists, computational, industrial and physical scientists to stimulate new inter-disciplinary research and collaboration in this area. Our website provides a useful additional level of information for our members and distributes information to members, other scientists and the general public will also augment these meetings. We also wish to facilitate new collaborative research programmes that will arise from this network by funding inter-laboratory and interdisciplinary visits for students, postdoctoral researchers and PIs, enabling technology and technique transfer to stimulate future research efforts within the UK scientific community.

Publications


10 25 50
 
Description Canada 
Organisation University of Guelph
Country Canada 
Sector Academic/University 
PI Contribution Research presentations and ideas
Collaborator Contribution A UK Canada consortium in the area of Bacterial Cell Walls. Mutual collaborative visits have been made.
Impact Joint grant applications
Start Year 2009
 
Description Research Collaboration 
Organisation University of Birmingham
Department College of Life and Environmental Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research collaboration leading to future grant applicationsResearch collaboration, student exchange
Impact Joint grant applications
Start Year 2008
 
Description Research Collaboration 
Organisation University of Newcastle
Department Institute of Cell and Molecular Biosciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research collaboration leading to future grant applicationsResearch collaboration, student exchange
Impact Joint grant applications
Start Year 2008
 
Title Peptidoglycan intermediates availible to Scientific community 
Description The BACWAN synthetic facility has developed a range of peptidoglycan intermediates that are available to the scientific community for use in research and assay development 
Type Support Tool - For Medical Intervention
Current Stage Of Development Initial development
Year Development Stage Completed 2008
Development Status Under active development/distribution
Impact These intermediates are already having an impact on advancing the development of novel assays and routes for antibiotic discovery as well as basic science 
 
Description Getting to grips with antibiotic resistance 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact The School of Life Sciences at Warwick hosted members of the public and press for a presentational evening with talks, lab tours and demonstrations in an event entitled: "Getting to grips with antibiotic resistance" This event was held in antibiotic awareness week in November 2016 and hosted around 90 visitor
Year(s) Of Engagement Activity 2016
URL http://www2.warwick.ac.uk/fac/sci/lifesci/outreach/next/
 
Description Press release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact Web cast and press release outlining work at Warwick and wider network

Invitation to speak, further public understanding of science presentations
Year(s) Of Engagement Activity 2008
 
Description School Visit - Hathersage 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Introduction to microbiology. This included oral and practical sessions.

No subsequent impact
Year(s) Of Engagement Activity 2009
 
Description School Visit Shrewsbury 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Schools visit and promotion

Invitation to return
Year(s) Of Engagement Activity 2009