Sheffield antimicrobial resistance network - SHAMROK
Lead Research Organisation:
University of Sheffield
Department Name: Physics and Astronomy
Abstract
The introduction of antibiotics in the 1940's revolutionised healthcare and underpinned medical advances through the rest of the century, but little over 70 years later we now face increasing instances of antimicrobial resistance that threaten many life-saving treatments. Problems with developing new innovative solutions to these challenges come from areas as diverse as a lack of understanding of the fundamental science explaining the mode of action of antimicrobials, to understanding clinical bottlenecks in the development of new treatments. If we are to be successful in developing new treatments and maintain our current precarious position in winning the war against bacterial infection, we need to understand and address these challenges fully. To do this will require innovative approaches that draw in expertise and cutting-edge methodology from the physical sciences and engineering, working in partnership with biologists and clinicians. The University of Sheffield has world-leaders in bacterial research, from microbiology to vaccine development and clinical practice, and a proven track record of close collaboration between Biologists, Medics, Chemists, Physicists and Engineers to address these problems. However, looking more widely the University has considerably more to offer through encouraging and developing new research collaborations that will fully engage those in Engineering and the Physical Sciences with the potential to help circumvent bottlenecks and problems.
This project aims to develop a framework to nurture and develop new research opportunities to augment those already in place as part of our internationally leading Imagine: Imaging Life and Florey Institutes. We will build an expansive, cross Faculty network that will focus on the EPSRC defined challenges we are best placed to address: the development of physical and physicochemical tools for understanding bacteriology and the host response ("Tools for understanding bacteriology"); and the development of new surfaces, dressings, and tissue engineering related approaches for preventing infections and delivering antimicrobials ("Improved drug delivery strategies for antimicrobials" and "Smart surfaces and dressings to prevent infection"). A series of focussed workshops, discipline hopping research and short proof-of-concept research projects will deliver new collaborations and solutions to a worldwide problem. We will aim to both take advantage of obvious synergies and to actively search deeper for new opportunities, making the most of our existing expertise to catalyse truly transformative activities that are unconstrained by traditional discipline boundaries.
This project aims to develop a framework to nurture and develop new research opportunities to augment those already in place as part of our internationally leading Imagine: Imaging Life and Florey Institutes. We will build an expansive, cross Faculty network that will focus on the EPSRC defined challenges we are best placed to address: the development of physical and physicochemical tools for understanding bacteriology and the host response ("Tools for understanding bacteriology"); and the development of new surfaces, dressings, and tissue engineering related approaches for preventing infections and delivering antimicrobials ("Improved drug delivery strategies for antimicrobials" and "Smart surfaces and dressings to prevent infection"). A series of focussed workshops, discipline hopping research and short proof-of-concept research projects will deliver new collaborations and solutions to a worldwide problem. We will aim to both take advantage of obvious synergies and to actively search deeper for new opportunities, making the most of our existing expertise to catalyse truly transformative activities that are unconstrained by traditional discipline boundaries.
Planned Impact
Antimicrobial resistance now poses an "apocalyptic threat" ((Dame Sally Davies, Chief Medical Officer, January 2013). It threatens to impact upon us all, and to tackle it requires input from across Medicine, Science and Engineering. By bridging the gaps between clinicians and bacteriologists working on AMR, and scientists and engineers with new techniques, technologies and approaches, we aim to develop the connections that will lead to transformative breakthroughs in tackling this problem.
SHAMROK is about making new connections, developing new collaborations through preliminary data, and discovering the bottlenecks that may seem intractable but that need to be addressed. As such, it will lead onto future research, collaboration and application that we expect to have real impact. Predicting where precisely this impact will lie at this stage is difficult, but in the area of AMR any inroads will provide benefit and save lives, so we expect the ultimate societal impact of the research to be great.
The management team are extremely experienced in translating their research into real impact, and will use this expertise to steer the new projects that are initiated. Foster was founder and is now CTO of Absynth Ltd, a spin-out company developing a vaccination approach to Staphylococcus aureus infection (as in the hospital super-bug MRSA). MacNeil has extensive experience of interdisciplinary research and of translating cell therapies from laboratory research to clinical use, including Myskin(TM) for diabetic ulcers and burns, and tissue engineered oral mucosa for reconstruction of urethral stricture. She brings a drive for translational benefit that will disseminate across the programme. Hobbs was a founding director of the high speed atomic force microscopy company Infinitesima Ltd, which now sells into the silicon fabrication market, and as such has experience of taking high technology products to the market. Dockrell is a practising clinician in infectious disease, bringing the "end-user" perspective to any developments that are made. This combined expertise in translational industrial interaction, from across the medicine/science/engineering market spaces, will underpin our pathways to impact and help to ensure that appropriate steps are taken early on so as to allow advances to reach their full potential.
SHAMROK is about making new connections, developing new collaborations through preliminary data, and discovering the bottlenecks that may seem intractable but that need to be addressed. As such, it will lead onto future research, collaboration and application that we expect to have real impact. Predicting where precisely this impact will lie at this stage is difficult, but in the area of AMR any inroads will provide benefit and save lives, so we expect the ultimate societal impact of the research to be great.
The management team are extremely experienced in translating their research into real impact, and will use this expertise to steer the new projects that are initiated. Foster was founder and is now CTO of Absynth Ltd, a spin-out company developing a vaccination approach to Staphylococcus aureus infection (as in the hospital super-bug MRSA). MacNeil has extensive experience of interdisciplinary research and of translating cell therapies from laboratory research to clinical use, including Myskin(TM) for diabetic ulcers and burns, and tissue engineered oral mucosa for reconstruction of urethral stricture. She brings a drive for translational benefit that will disseminate across the programme. Hobbs was a founding director of the high speed atomic force microscopy company Infinitesima Ltd, which now sells into the silicon fabrication market, and as such has experience of taking high technology products to the market. Dockrell is a practising clinician in infectious disease, bringing the "end-user" perspective to any developments that are made. This combined expertise in translational industrial interaction, from across the medicine/science/engineering market spaces, will underpin our pathways to impact and help to ensure that appropriate steps are taken early on so as to allow advances to reach their full potential.
Organisations
Publications
Deroy C
(2022)
Reconfigurable Microfluidic Circuits for Isolating and Retrieving Cells of Interest.
in ACS applied materials & interfaces
Meacock O
(2020)
Bacteria solve the problem of crowding by moving slowly
in Nature Physics
Meacock O
(2023)
Tracking bacteria at high density with FAST, the Feature-Assisted Segmenter/Tracker
in PLOS Computational Biology
Nwokeoji AO
(2019)
Analysis of long dsRNA produced in vitro and in vivo using atomic force microscopy in conjunction with ion-pair reverse-phase HPLC.
in The Analyst
Oliveira NM
(2022)
Suicidal chemotaxis in bacteria.
in Nature communications
Pasquina-Lemonche L
(2020)
The architecture of the Gram-positive bacterial cell wall.
in Nature
Turner RD
(2018)
Molecular imaging of glycan chains couples cell-wall polysaccharide architecture to bacterial cell morphology.
in Nature communications
Vasilev C
(2022)
FRET measurement of cytochrome bc1 and reaction centre complex proximity in live Rhodobacter sphaeroides cells.
in Biochimica et biophysica acta. Bioenergetics
Description | This was a network grant which funded a large range of pump priming projects which have led to multiple new collaborations and grant applications. |
Exploitation Route | There is the possibility of development of new anti-microbials, new approaches for enhancing innate immune response, and new surface treatments etc to reduce the spread of bacteria without the need for antimicrobials, which all currently being explored in follow-on work from the pump priming projects funded. |
Sectors | Healthcare Manufacturing including Industrial Biotechology |
Description | Work on DNA led to some work on RNA characterisation for complementing HPLC analysis. This has led to a paper, and a short (3 month) contract with a company. Our work on the organisation of membrane proteins was picked up and used as part of a "comment" in the journal Cell, https://doi.org/10.1016/j.cell.2019.10.023 . |
First Year Of Impact | 2019 |
Sector | Agriculture, Food and Drink,Energy |
Impact Types | Economic |
Description | A Matter Of Life Or Death - An Integrated Understanding Of MRSA |
Amount | £5,990,700 (GBP) |
Funding ID | 227233/Z/23/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2024 |
End | 12/2029 |
Description | The Physics of Antimicrobial Resistance |
Amount | £2,158,027 (GBP) |
Funding ID | EP/T002778/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2022 |
Description | The bacterial cell wall in life and death |
Amount | £1,649,282 (GBP) |
Funding ID | 212197/Z/18/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2019 |
End | 12/2023 |
Title | Correlative Super-Resolution Optical and Atomic Force Microscopy Reveals Relationships Between Bacterial Cell Wall Architecture and Synthesis in Bacillus subtilis - Raw data repository |
Description | This is the raw data corresponding to the article published in ACS Nano by the authors. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://figshare.shef.ac.uk/articles/dataset/Correlative_Super-Resolution_Optical_and_Atomic_Force_M... |
Title | Correlative Super-Resolution Optical and Atomic Force Microscopy Reveals Relationships Between Bacterial Cell Wall Architecture and Synthesis in Bacillus subtilis - Raw data repository |
Description | This is the raw data corresponding to the article published in ACS Nano by the authors. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://figshare.shef.ac.uk/articles/dataset/Correlative_Super-Resolution_Optical_and_Atomic_Force_M... |
Title | Raw data for 'Bacteria solve the problem of crowding by moving slowly' |
Description | These .zip files contain the raw data associated with the manuscript 'Bacteria solve the problem of crowding by moving slowly' (Meacock, O.J., Doostmohammadi, A., Yeomans, J.M., Foster, K.R., Durham, W.M., 2020). The contents consists of the following folders:
- Cell morphology data: Data used to measure the length of WT and pilH cells at exponential-phase in liquid culture and in the monolayer. Used in Extended Data Fig. 6a.- Liquid culture competition CFUs: Spreadsheet containing the raw CFU counts associated with Extended Data Fig. 8b.- Low-density cell tracks: Tracks used to measure motility and shape of strains under low density subsurface conditions. Used in Extended Data Figs. 1c, 3b, 6a, 9d.- Monolayer cell and defect tracks: Defect and cell tracks from high-density WT and pilH subsurface monolayers. Used in Figs. 1g, 3e-f, Extended Data Figs. 3a and 4.- Raw confocal microscopy data: Raw confocal imaging files of surficial and subsurficial colonies. Used in Fig. 1d, Extended Data Fig. 2a.- Raw edge composition snapshots: Raw images used to generate Fig. 2g, Extended Data Fig. 10c-e.- Raw high-resolution rosette data: Raw and partially processed imaging data associated with the rosettes presented in Fig. 4d-f and Extended Data Fig. 7.- Subsurface colony composition and packing fraction data: Spreadsheets containing measurements of colony edge position, edge population composition and edge packing fraction, used to generate Fig. 2c-e, Extended Data Figs. 9b,c, 10a,b.- Subsurface colony edge coordinates: Spreadsheets containing measurements of colony edge position, used to generate Fig. 1f,g, Extended Data Fig. 1a,b.- Surficial colony composition measurements: Raw CFU counts and images used to generate Fig. 2a,b. For further details on the format of individual files, please refer to the readme.txt files in each folder. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://figshare.shef.ac.uk/articles/dataset/Raw_data_for_Bacteria_solve_the_problem_of_crowding_by_... |