BBSRC David Phillips Fellowship: Growth and development of bacterial 3-dimensional structures - A multidisciplinary approach
Lead Research Organisation:
University of Southampton
Department Name: Centre for Biological Sciences
Abstract
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Technical Summary
The objective of this research is to integrate approaches to the study of autonomously replicating cells in confined environments (here we consider malignancies and surface-attached bacteria). It is proposed that the evolutionary and ecological pressures for growth in these taxonomically very different systems are fundamentally the same, and thus can be addressed within the same experimental and conceptual framework. Processes of interest in tumorigenesis include i) destabilisation if the cancer cell genome, ii) viral-host cell interactions (in certain cancers) and iii) differentiation and death of cancer cells inside tumours. This project will integrate approaches to bacterial and tumour development by studying these processes in 3-dimensional structures in bacterial biofilms.
Organisations
People |
ORCID iD |
| Jeremy Webb (Principal Investigator) |
Publications
Barraud N
(2009)
Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal.
in Journal of bacteriology
Barraud N
(2012)
Cephalosporin-3'-diazeniumdiolates: targeted NO-donor prodrugs for dispersing bacterial biofilms.
in Angewandte Chemie (International ed. in English)
Barraud N
(2009)
Nitric oxide-mediated dispersal in single- and multi-species biofilms of clinically and industrially relevant microorganisms.
in Microbial biotechnology
Conibear TC
(2009)
Role of mutation in Pseudomonas aeruginosa biofilm development.
in PloS one
Fagerlind MG
(2012)
Dynamic modelling of cell death during biofilm development.
in Journal of theoretical biology
Jefferies JM
(2011)
Risk of red queen dynamics in pneumococcal vaccine strategy.
in Trends in microbiology
McElroy KE
(2014)
Strain-specific parallel evolution drives short-term diversification during Pseudomonas aeruginosa biofilm formation.
in Proceedings of the National Academy of Sciences of the United States of America
Penn AS
(2012)
Can Simpson's paradox explain co-operation in Pseudomonas aeruginosa biofilms?
in FEMS immunology and medical microbiology
Schleheck D
(2009)
Pseudomonas aeruginosa PAO1 preferentially grows as aggregates in liquid batch cultures and disperses upon starvation.
in PloS one
| Description | This grant has provided new insight into the mechanisms by which antibiotic resistant biofilms grow and develop, thereby offering new strategies for the control of problematic chronic infections. The Fellowship award has enabled me to build on my discovery that nitric oxide is an important signal that causes the breakup of bacterial biofilms, which has led to a patent, clinical trial, publication and follow-on funding outputs. |
| Exploitation Route | The findings provide novel strategies for the control of biofilms in both environmental and clinical settings. They are being exploited clinically as a strategy to control certain types of antibiotic resistant infection, for example respiratory infections in cystic fibrosis patients. |
| Sectors | Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Proof of concept clinical trial for the treatment of biofilm-associated infection in cystic fibrosis. UK NHS REC 11/H0502/7, EudraCT 2010-023529-39 |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Respiratory Biomedical Research Unit (BRU) (Includes core-funded biofilm program that follows BBSRC David Philips Fellowship). |
| Amount | £6,000,000 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2009 |
| End | 12/2012 |
| Title | Methods and Compositions for Regulating Biofilm Development |
| Description | The present invention relates to methods for promoting dispersal of, or preventing formation of microbial biofilms, comprising: exposing a biofilm to an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent; treating a surface or medium susceptible to biofilm formation with an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent; incorporating an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent in a surface or medium susceptible to biofilm formation; or inducing the accumulation of one or more reactive oxygen or nitrogen species within microorganisms within said biofilm or capable of forming a biofilm. The invention also relates to methods for maintaining or enhancing or maintaining and enhancing the functioning of a biofilm, comprising exposing a biofilm to at least one nitric oxide scavenger, at least one antioxidant or at least one nitric oxide scavenger and at least one antioxidant. The invention also relates to compositions for promoting dispersal of, or preventing formation of microbial biofilms, or for maintaining or enhancing or maintaining and enhancing the functioning of microbial biofilms. |
| IP Reference | US2009214674 |
| Protection | Patent granted |
| Year Protection Granted | 2009 |
| Licensed | Commercial In Confidence |
| Impact | Pilot scale clinical trials for new therapies to treat microbial biofilm infection in cystic fibrosis patients. |