No Own Goal: reducing biofouling using surface engineering
Lead Research Organisation:
University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci
Abstract
Keyword:Biofilms
Bacteria can attach to surfaces and form massive aggregates called biofilms. Such collections can build up on natural surfaces within the body, or on urinary catheters or other implanted devices, and lead to hard-to-treat infections. There is an urgent need for materials that resist attachment as over 80% of people receiving a catheter develop a urinary tract infection that requires antibiotic treatment. These infections cost the NHS between £1.0-2.5 billion and accounts for around 2100 deaths per year (Feneley et al., 2015). Moreover, the bacteria associated with such infections are developing widespread resistance, so the problem is predicted to get worse.
In this multidisciplinary project, we combine knowledge of how to manipulate the topography of a material at the nanoscale with the detailed understanding of how bacteria attach to a given surface. We will use a clinically-relevant E. coli strain associated with catheter infections as a model organism. We will correlate how changes in the surface texture can affect gene expression and attachment of bacteria using a combination of microscopy (live cell imaging) and transcriptomics in conjunction with mutations in adhesion and secretory pathways. This will assist us in building a map of how we potentially can benefit from synergistic effects of surface patterning and existing antibiotic therapies.
The EPSRC strives to foster and support innovation and leadership within the scientific field and we believe this project aligns impeccably with these objectives. The study of bacterial gene expression in response to engineered surfaces is a new and underexplored field with huge potential benefits and a vast array of possible practical application. From medical implants and sterility control of laboratory surfaces to improved assays and culturing techniques, improved understanding of this area would positively impact patient care and organism control in the UK and abroad. The EPSRC aims to promote a balanced and collaborative approach to solving modern scientific issues and our approach matches this goal, combining two distinct but highly complementary scientific disciplines to creatively solve a highly relevant biomedical problem.
The EPSRC also aims to nurture the next generation of researchers and innovators. This project will also the student to gain invaluable multidisciplinary training and experience. Their work in a microbiology based laboratory they will gain skills in genetic engineering, transcriptomics, high-throughput assay development and bioinformatic analysis. Their work as part of a nanoengineering team will grant them experience and training in nanofabrication, microfluidics and computer based modelling. These different environments will give them the opportunity to gain a unique and highly valuable skillset that will not only allow them to complete this project but will prepare them for the next steps in their research career.
Bacteria can attach to surfaces and form massive aggregates called biofilms. Such collections can build up on natural surfaces within the body, or on urinary catheters or other implanted devices, and lead to hard-to-treat infections. There is an urgent need for materials that resist attachment as over 80% of people receiving a catheter develop a urinary tract infection that requires antibiotic treatment. These infections cost the NHS between £1.0-2.5 billion and accounts for around 2100 deaths per year (Feneley et al., 2015). Moreover, the bacteria associated with such infections are developing widespread resistance, so the problem is predicted to get worse.
In this multidisciplinary project, we combine knowledge of how to manipulate the topography of a material at the nanoscale with the detailed understanding of how bacteria attach to a given surface. We will use a clinically-relevant E. coli strain associated with catheter infections as a model organism. We will correlate how changes in the surface texture can affect gene expression and attachment of bacteria using a combination of microscopy (live cell imaging) and transcriptomics in conjunction with mutations in adhesion and secretory pathways. This will assist us in building a map of how we potentially can benefit from synergistic effects of surface patterning and existing antibiotic therapies.
The EPSRC strives to foster and support innovation and leadership within the scientific field and we believe this project aligns impeccably with these objectives. The study of bacterial gene expression in response to engineered surfaces is a new and underexplored field with huge potential benefits and a vast array of possible practical application. From medical implants and sterility control of laboratory surfaces to improved assays and culturing techniques, improved understanding of this area would positively impact patient care and organism control in the UK and abroad. The EPSRC aims to promote a balanced and collaborative approach to solving modern scientific issues and our approach matches this goal, combining two distinct but highly complementary scientific disciplines to creatively solve a highly relevant biomedical problem.
The EPSRC also aims to nurture the next generation of researchers and innovators. This project will also the student to gain invaluable multidisciplinary training and experience. Their work in a microbiology based laboratory they will gain skills in genetic engineering, transcriptomics, high-throughput assay development and bioinformatic analysis. Their work as part of a nanoengineering team will grant them experience and training in nanofabrication, microfluidics and computer based modelling. These different environments will give them the opportunity to gain a unique and highly valuable skillset that will not only allow them to complete this project but will prepare them for the next steps in their research career.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509668/1 | 01/10/2016 | 30/09/2021 | |||
| 1954240 | Studentship | EP/N509668/1 | 01/10/2017 | 30/09/2021 | James Mordue |
| EP/R513222/1 | 01/10/2018 | 30/09/2023 | |||
| 1954240 | Studentship | EP/R513222/1 | 01/10/2017 | 30/09/2021 | James Mordue |
| Description | There are still several major experiments to complete within the project but so far some conclusions that can be drawn are: 1) There are large differences in biofilm phenotypes within the same strain with even minor changes to the environment. Even changing nothing but the size of the well bacteria are grown in can significantly alter their measured biofilm production. (eg. biofilm growth ability in a 96 well plate isn't always a good predictor of growth in a 12 well plate) 2) An RNA sequencing experiment showed there are large differences between attached and planktonic bacterial gene expression. This is true even when the same bacteria are grown under exactly the same conditions within the same well. The project is ongoing and further findings are expected. |
| Exploitation Route | These results can be used to inform and improve to design of future experiments in this area. Careful control and selection of the growth environment is essential for the study of attachment and biofilm phenotypes. What has been learned in this area of the project so far could be invaluable in future work. Differentially expressed genes between attached and planktonic bacteria observed in this project can be used as the targets of further study and investigation. Their contributions to biofilms and attachment phenotypes more generally could be extremely interesting. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Microbiology Society Conference Grant |
| Amount | £240 (GBP) |
| Funding ID | GA001888 |
| Organisation | Microbiology Society |
| Sector | Learned Society |
| Country | United Kingdom |
| Start | 03/2020 |
| End | 04/2020 |
| Title | GFP gene reporters |
| Description | These are GFP gene reporter plasmids. They can be used to transform E. coli bacteria, allowing them to produce fluorescent GFP molecule when they use promoters of several genes associated with attachment and biofilm formation. Construction of these reporters came about after we found several genes that were highly differentially expressed between attached and planktonic bacteria. They were made to allow the monitoring of the activity of these genes in culture. |
| Type Of Material | Cell line |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | These reporters have allowed the project to progress and pursue the roles of these genes in attachment to different surfaces. |
| Title | Knockout strains |
| Description | These are strains of urinary pathogenic Escherishia coli that have had one of two genes knocked out. These genes (soxS and trxC) where found to be highly differentially expressed between attached and planktonic bacteria. In order to better understand the roles of these genes in attachment and biofilm formation they were knocked out by lambda red recombination. |
| Type Of Material | Cell line |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | This has allowed for the study of the roles these genes have in attachment and biofilm formation. They will later be used in combination with nanopatterned surfaces to study their roles in attachment to these surfaces. |
| Description | Undergraduate poster presentations |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Interactive poster sessions attended by approximately 50 undergraduate student. Scientific posters were presented by those doing the research and students were encouraged to ask questions about both the project and what a career in research is like. The main outcome of this was to better inform students about what a research career is like and help them decide if it is a career path they'd be interested in following. |
| Year(s) Of Engagement Activity | 2018,2019 |