BBSRC David Phillips Fellowship: Growth and development of bacterial 3-dimensional structures - A multidisciplinary approach

Lead Research Organisation: University of Southampton
Department Name: School of 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.

Publications

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Penn AS (2012) Can Simpson's paradox explain co-operation in Pseudomonas aeruginosa biofilms? in FEMS immunology and medical microbiology

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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

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Jefferies JM (2011) Risk of red queen dynamics in pneumococcal vaccine strategy. in Trends in microbiology

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Fagerlind MG (2012) Dynamic modelling of cell death during biofilm development. in Journal of theoretical biology

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Barraud N (2012) Cephalosporin-3'-diazeniumdiolates: targeted NO-donor prodrugs for dispersing bacterial biofilms. in Angewandte Chemie (International ed. in English)

 
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
First Year Of Impact 2010
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 patent relates to methods for promoting dispersal of, or preventing formation of microbial biofilms using nitric oxide. 
IP Reference US8425945 
Protection Patent granted
Year Protection Granted 2013
Licensed Commercial In Confidence
Impact Pilot scale clinical trials for new therapies to treat microbial biofilm infection in cystic fibrosis patients.