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National Research Symposium Bridging the Gaps between Engineering and Physical Sciences and Antimicrobial Resistance 14-15 June 2017 Warwick Arts Centre, Coventry, CV4 7AL

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Welcome “On behalf of the INTEGRATE network, I would like to warmly welcome you to Warwick. I'm very much looking forward to meeting you all, and hearing about your work. I hope that this symposium can lead to some exciting and fruitful collaborations between the different Universities.” Professor Matt Keeling, joint Professor between the School of Life Sciences and the Mathematics Institute at the University of Warwick, Director of the Zeeman Institute

Outreach Programme Wednesday 14 June 2017

Times Wednesday 14 June Location

17:00-18:50

Outreach activities - Antibiotics Unearthed - 3D Virtual Reality Protein Explorer - Electronic Nose - Surgeon X - Science Speakers - Gram Stains

Foyer

19:00-20:00 Welcome Address and Dinner Helen Martin Studio

20:00-20:15 Dinner Speaker: Sara Kenney (Surgeon X) Helen Martin Studio

20:15-20:30 Dinner Speaker: Paul Cooke (CATCH) Helen Martin Studio

20:30-21:00 Film Screening (CATCH) Helen Martin Studio

21:00-21:30 Networking Helen Martin Studio

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Outreach Stands Stand 1: Surgeon X Surgeon X is a new comic exploring the antibiotic apocalypse from the perspective of a brilliant vigilante doctor. Come to our interactive stand to Meet comic writer and film director Sara Kenney. Find Out more about the striking premise of this medical thriller, set in a near-future London where antibiotics no longer work. Have a Go on the Surgeon X Enhanced Comic multi-content app. Stand 2: Microbe Discovery Zone Make the unseen seen – it’s science not magic. Since their invention by Robert Hooke in 1665, microscopes have been an indispensable tool of biology, revealing the existence of cells and living forms too small to see with our naked eye. Meet early career microbiologists working out new ways to combat infections. Find out about the different types of bacteria and how doctors and other health professionals recognise them. Have a Go on the microscope, and see if you too can spot the difference between ‘Gram-positive’ and ‘Gram-negative’ bugs – What might this mean for patients? Stand 3: Electronic Nose – Sniffing out Disease E-noses work on a similar principal to the human nose, recognising smells by their unique aroma. Researchers at the Warwick Biomedical Sensors Laboratory developed the first commercial electronic nose (e-nose) in the early 1990’s. Since then e-noses have used in a variety of applications – telling if food has gone off, or if someone is suffering from a bacterial chest infection.

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At the E-nose stand, you can Meet researchers from the Biomedical Sensors Lab. Have a Go breathing into our e-nose device and see what it picks up. Find out more about ongoing research into sniffing out disease and how this could help reduce inappropriate use of antibiotics. Stand 4: Antibiotics Unearthed Could the next antibiotic be in your garden? The Antibiotics Unearthed project gives the public, students and teachers a chance to work alongside scientists to discover new antibiotics from the bacteria in soil. Meet scientists involved in the project. Find out more about the need for new antibiotics and why it is so hard to make them. Have a Go at discovering new antibiotics from the soil around us – we’ll talk you through the steps. Stand 5: 3D Protein Explorer Proteins are the building blocks of life, vital to our existence and found in all organisms. Meet physicists working to solve the structure and mechanisms of proteins to better understand how the antibiotic Penicillin works. Put on our virtual reality headset and Have a Go at playing with proteins in 3D. Pick them up, spin them, throw them… And Find out how virtual reality could help us create the next antibiotic. Stand 6: Science Speakers Find out why Antibiotic Resistance is one of the greatest challenges we face and requires the combined effort of the public, government, doctors and researchers from all disciplines. Meet researchers from different fields working together to make a difference. Have a go challenging our speakers with any questions you may have, and feel free to spark a debate - Our scientists are here to hear your thoughts

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Dinner Speakers Sara Kenney, Surgeon X Surgeon X is a debut comic by writer and filmaker Sara Kenney, funded by Wellcome Trust arts grant. The setting is a dystopian London in the near future, where antibiotics no longer work. Rosa Scott is a brilliant NHS surgeon gone rogue, a vigilante doctor who uses experimental surgery and black market drugs to treat patients. Dr Harriet Palfreyman, a professional historian at the University of Manchester, was responsible for advising Surgeon X’s wider world, taking inspiration from past health crises such as the 1665 plague epidemic in London.

Paul Cooke, CATCH CATCH is set in a near future, where all antibiotics have stopped working. The film follows a father, Tom, and his daughter, Amy, quarantined in their house during a lethal bacterial pandemic. Their fragile existence is threatened when one of them gets sick. First-time directors Paul Cooke and Dominic Rees-Roberts present the crucial issue of antibiotic resistance as a story that might so easily be part of our children's future. Professor Tim McHugh, a TB researcher at UCL, was one of the scientific advisors on the film.

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Research Programme Thursday 15 June 2017 Times Wednesday 14 June Location 08:00-08:45 Registration and Poster Setup Foyer/Marquee

08:50-09:00 Welcome Address Woods Scawen Room

09:00-09:30 Keynote Speaker: Dr Richard Seabrook (Medicines Discovery Catapult)

Woods Scawen Room

Session 1: Improving Healthcare 09:30-10:30

09:30 Bruce Savage (GCF Diagnostics) 09:45 Elizabeth Beech (NHS Improvement) 10:00 Dr Abid Hussain (PHE) 10:15 Dr Esther Robinson (PHE)

Woods Scawen Room

10:30-11:00 Coffee and Posters Marquee Session 2: Exploring New Antibiotics 11:00-11:45

11:00 Dr Ricky Cain (Warwick) 11:15 Prof Ian Gilbert (Dundee) 11:30 Dr Danish J. Malik (Loughborough)

Woods Scawen Room

11:45-12:30 Lunch Marquee

Session 3: Detection & Diagnostics 12:30-14:00

12:30 Dr Veeren Chauhan (Nottingham) 12:45 Prof Thomas Krauss (York) 13:00 Dr Charlotte Bermingham (Bristol) 13:15 Break / Q&A 13:30 Dr Sourav Ghosh (Loughborough) 13:45 Dr Geetha Srinivasan (Belfast)

Woods Scawen Room

14:00-14:30 Coffee and Posters Marquee

14:30-15:15 Network Overviews

14:30 Prof Tim Leighton (Southampton) 14:45 Sandip Kumar (Sheffield) 15:00 Dr Patrick SM Dunlop (Ulster)

Woods Scawen Room

Session 4: Biofilms, Infection Control & Modelling 15:15-16:45

15:15 Dr Esther Karunakaran (Sheffield) 15:30 Dr Michele Barbour (Bristol) 15:45 George Parry (Warwick) 16:00 Dr Robert Hyde (Nottingham) 16:15 Prof Bill Graham (Belfast) 16:30 Dr Ben Collyer (Warwick)

Woods Scawen Room

16:45-18:00 Networking and Drinks Marquee

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Keynote Speaker Dr Richard Seabrook, Medicines Discovery Catapult Technology Transforming AMR Richard Seabrook is currently CEO of the advisory company 360Biomedical Ltd, Senior Advisor for both Wellcome Trust and also the Medicines Discovery Catapult, a board member of the Global Health Innovation Technology Fund, and an Advisor to St George’s University of London. Previously, he was Head of Business Development at the Wellcome Trust, where he lead on £750M translational funding. This included the £200M international Seeding Drug Discovery Fund – encompassing the discovery of Plazomicin, Polycap, Ridinilazole and Xanamem. He has also overseen the foundation of SMEs and their development through progressive funding rounds. Richard has led on multiple licensing transactions with pharma, most recently with Basilea, GSK, Johnson & Johnson, MSD, Merck-Serono and Novartis.

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Session 1: Improving Healthcare 09:30-10:30 Chair: Dr Meera Unnikrishnan, Warwick Medical School Times Speaker Affiliation 09:30 Bruce Savage GFC Diagnostics

“MicroScreen Technology for AMR Detection” 09:45 Elizabeth Beech NHS Improvement “Reducing inappropriate antimicrobial prescribing by 50% by 2020 – can we

do it?” 10:00 Dr Abid Hussain PHE

“Antimicrobial resistance in clinical practice: challenges and aspirations” 10:15 Dr Esther Robinson PHE

“Targets in E. coli bloodstream infection: implications for AMR” Session 1 Speakers Bruce Savage, GFC Diagnostics “MicroScreen Technology for AMR detection” Bruce Savage graduated with a life science degree from London University and spent 6 years in drug development with Roche pharmaceuticals. He then spent many years in sales and marketing positions in the medical diagnostics industry before going on to found a molecular diagnostics company called Cytocell about 20 years ago. Subsequently he then went on to help found a further 6 bioscience companies. He is the co-founder and CEO of GFC Diagnostics. Abstract: GFC Diagnostics is a small medical diagnostics company focussed on development of point of care tests for detection of smoking and antimicrobial resistance. It currently sells a test called IsoScreen for detection of compliance with the antibiotic isoniazid for anti-TB therapy. Non-compliance is causing a rise in resistance. The Longitude prize is offering £8m for development of informative, accurate, affordable rapid point of care test that is easy to use anywhere in the world. GFC Diagnostics are in the process of developing such a test. It is based on their SafeTube device and uses proprietary DNA probe hybridisation with amplification technology. The test takes 30 minutes, produces a coloured end product and is easy to use. The test will be described and data shown on its performance for detection of MRSA. The company is starting to extend the range of rapid tests for other antibiotic resistance organisms and hopes to apply for the Longitude prize next year. It is the winner of a Discovery award from the prize committee. Elizabeth Beech, NHS Improvement “Reducing inappropriate antimicrobial prescribing by 50% by 2020 – can we do it?” Elizabeth Beech trained as a pharmacist in Birmingham and has worked in variety of organisations throughout the NHS, in many different clinical roles including academia and research. Elizabeth is currently seconded to the Patient Safety team in NHS Improvement as a national project lead (England) for healthcare associated infections & Antimicrobial Resistance. She also works for NHS Bath and North East Somerset CCG as a prescribing advisor, where she also leads AMR, Acute Kidney Injury, and safer care culture work programmes. This includes #ToDipOrNotToDip a Quality Improvement programme to improve the

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management of UTI in care homes - this has a growing community of interest #TDONTD on Slack. She is proud to be part of the Q community loves collaboration!

Dr Abid Hussain, PHE “Antimicrobial resistance in clinical practice: challenges and aspirations” Abid Hussain is employed by Public Health England as a full-time Consultant Medical Microbiologist embedded at the Heart of England Foundation Trust. Currently, he is the Director of Infection Prevention and Control which includes responsibility for healthcare associated infections (HCAI) and antimicrobial stewardship. He is also the Clinical Lead for the microbiology service as well as the Technical Lead for the diagnostic microbiology laboratory. Abid Hussain also holds an Honorary Senior Clinical Lecturer and Examiner position at the University of Birmingham. His current research interests include behaviour modification in relation to hand hygiene, rapid diagnostics for sepsis and molecular typing.

Dr Esther Robinson, PHE “Targets in E. coli bloodstream infection: implications for AMR” Esther Robinson is a Public Health Microbiologist at Public Health England and a consultant microbiologist at Heart of England NHS Trust in Birmingham. She is an Honorary Clinical Associate Professor at Warwick Medical School. Research interests include antimicrobial stewardship, genetics of antibiotic resistance and bringing genomic epidemiology into clinical practice, with a particular interest in TB. Abstract: Escherichia coli (E. coli) is a Gram- negative bacterium that is a common cause of bloodstream infection (bacteraemia). Public Health England (PHE) has collected data from mandatory surveillance of these infections since 2011 and rates of bacteraemia have been rising in England. The NHS in England has now been set an ambitious target to reduce E. coli bacteraemia by 50% by 2021. It is likely that similar targets will follow for other causes of gram- negative bacteraemia. This is on a background of rising rates of antimicrobial resistance, with gram-negative organisms being a particular concern. The NHS also has quality targets to reduce prescribing of antimicrobials, with particular focus on antimicrobials used to treat gram- negative infections in hospitals. A number of interventions have been proposed to help the NHS meet the target. Changes in antimicrobial prescribing and infection prevention may be of benefit, but evidence is often lacking and unintended consequences need to be considered

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Session 2: Exploring New Antibiotics 11:00-11:45 Chair: Prof Christopher Dowson, School of Life Sciences Times Speaker Affiliation 11:00 Dr Ricky Cain Warwick

“Multi-Targeting of tRNA synthetases: A paradigm shift in combating Antimicrobial Resistance”

11:15 Prof Ian Gilbert Dundee “Overview of the University of Dundee Drug Discovery Unit”

11:30 Dr Danish J. Malik Loughborough “Encapsulation of purified bacteriophages for targeted controlled release of

novel narrow spectrum antibiotics” Session 2 Abstracts Dr Ricky Cain, University of Warwick Life Sciences and Chemistry “Multi-Targeting of tRNA synthetases: A paradigm shift in combating Antimicrobial Resistance” Aminoacyl tRNA synthetases play a key role in protein synthesis acylating tRNA with the correct amino acid. Errors in this process lead to defects in protein folding and function leading to cell death. Each of the 20 amino acids has its own synthetase but some of these enzymes lack the ability to select the correct amino acid initially and are reliant on their “editing activity” to produce the correct aminoacyl tRNA liganded product. This editing process could be disrupted and thus produce a new line of antimicrobial chemotherapy which is less likely to be overcome by resistance through mutation since these potential drugs would require simultaneous mutations in multiple genes to afford resistance. The objective of this project is to obtain a structural data set of selected bacterial enzymes in amino-acyl site mimetics. We have made significant progress in this respect and have been able to design a probe compound set to investigate selectivity between the human and bacterial forms of the seryl aminoacyl tRNA synthetases and to further explore the potential of the probe for multi-targeting against other aminoacyl t-RNA synthetases. Chemical probe compounds were designed based upon the tRNA synthetase enzyme complex with sulfonyl adenylates from this study. The probes were utilizing d and biologically evaluated against the tRNA synthetase using a phosphate exchange based assay. The probes were observed to inhibit the bacterial forms of the enzyme with IC50s in the low micromolar range and appear to have selectivity over the corresponding human enzyme with probes exhibiting an IC50 in the millimolar range. These probes have been tested against the other selected bacterial tRNA synthetases to determine their ability to duel target however this testing has proved unsuccessful. In conclusion a novel class of probes has been designed and utilizing d which provide selectivity for the bacterial over mammalian forms of the enzyme yielding the potential for the design of new therapeutics. The lack of ability to multi-target different synthetases is a limitation which is planned to be overcome by further rounds of structure based drug desig utilizing different identified regions within the active site. 1-sentence summary of the link to AMR:

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The multi-targeting approach employed in this research should mean that if a mutation occurs in one aminoacyl tRNA synthetase, making it resistant to the designed inhibitors, the inhibitor will still be active against other aminoacyl-tRNA synthetases, thus still inhibiting protein synthesis and overcoming antimicrobial resistance. Prof Ian Gilbert, University of Dundee Division of Biological Chemistry and Drug Discovery “Overview of the University of Dundee Drug Discovery Unit” The University of Dundee Drug Discovery Unit is a fully operational, fully integrated drug discovery group working across multiple disease areas. We collaborate with partners to translate world-class biology research into novel drug targets and candidate drugs to address unmet medical need across our two areas of activity, Diseases of the Developing World and Innovative Targets Portfolio. Dr Danish J Malik, Loughborough University Chemical Engineering, Infection, Immunity and Inflammation “Encapsulation of purified bacteriophages for targeted controlled release of novel narrow spectrum antibiotics” Objectives: The aim of the work was to evaluate the use of novel microfluidic and membrane based techniques for encapsulation of purified (using ultrafiltration and ion exchange) bacteriophages in stimuli responsive polymers (microparticles) and liposomes (microparticles and nanoparticles) for treating multi-drug resistant gastrointestinal infections. Methods: Bacteriophage K (lytic, S. aureus, myovirus) and Felix O1 (lytic, S. enterica, myovirus) were used in the study. Phages were amplified using a Sartorius Biostat® operated in batch mode. Phages were purified using centrifugation, ultrafiltration, anion exchange chromatography and size exclusion chromatography to remove host cell proteins and host cell DNA. Encapsulation of SYBR green labelled phage in micro- and nanoparticles was shown using confocal microscopy. TEM imaging of encapsulated phage in liposomes was carried out. Phage stability upon exposure (exposure time > 2hr at pH 2) to simulated gastric fluid and subsequent phage release kinetics was studied using simulated intestinal fluid (phage titre measured using plaque assay). The effects of formulation (e.g. polymer or lipid composition), phage titre and experimental setup conditions were investigated on phage encapsulation, phage viability and storage stability. The phages were also spray dried and freeze dried using excipients to improve long-term storage stability. Results: We show that we can achieve significant concentration of highly purified phages (~1012 PFU/ml) using downstream processing operations by removing host cell proteins and host cell DNA. We have proof-of-principle results demonstrating controlled encapsulation of phages in pH responsive polymeric microparticles and liposomal micro- and nanoparticles using microfluidic and membrane encapsulation techniques. Our approach allowed precise control over phage loading per particle (i.e. control over phage dose). We show how scalable production of highly uniform micro- and nanoparticles may be achieved using membrane emulsification with control over particle size through manipulation of membrane shear and fluid properties (e.g. viscosity). Through changes to the formulation and the particle size, we also demonstrate control over the release dynamics (burst and sustained release formulations) of the phages in response to a pH or enzyme trigger. We demonstrate that encapsulated phages may be stored under refrigerated conditions following drying by addition of disaccharides such as trehalose as excipients. Conclusions: We have demonstrated that novel microfluidic and membrane based processes can be successfully used to encapsulate phages in stimuli responsive micro- and nanoparticles. These systems would allow delivery of phages to the gastrointestinal tract giving unprecedented control over the phage dose and the release profile to treat multi-drug resistant infections.

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Session 3: Detection & Diagnostics 12:30-14:00 Chair: Prof Tony McNally, Warwick Manufacturing Group Times Speaker Affiliation 12:30 Dr Veeren Chauhan Nottingham

“Gold-Aptamer-Nanoconstructs Engineered to Diagnose the Common Cold”

12:45 Prof Thomas Krauss York “Nanophotonic Antimicrobial Susceptibility test”

13:00 Dr Charlotte Bermingham Bristol Break/Q&A

13:15 “Analytical approach of Antibiotics as co-selective drivers for antimicrobial

resistance development and spread” 13:30 Dr Sourav Ghosh Loughborough “A non linear acoustic sensor for rapid phenotypic bacterial identification

and antibiotic susceptibility.” 13:45 Dr Geetha Srinivasan Belfast

“Novel Electronic devices for Healthcare Applications” Session 3 Abstracts Dr Veeren Chauhan, University of Nottingham Advanced Materials and Healthcare Technologies “Gold-Aptamer-Nanoconstructs Engineered to Diagnose the Common Cold” There is an immediate unmet need for a diagnostic technology that assists GPs and healthcare professionals when making point of care clinical prescribing decisions for respiratory tract infections (RTIs). Currently there is no easy to use low-cost desktop product that is able to stratify patients presenting with the symptoms of a RTI from viral or bacterial aetiology during the timeframe of typical GP-Patient consultation. As a result, antibiotics are overprescribed and have contributed to the rise of antimicrobial resistance, which is associated with both long-term medical and economic uncertainty. Existing solutions fall outside of the limited GP-Patient consultation timeframe (PCR, microscopy), require specialist skills to operate them (PCR, microscopy and ELISA) and are expensive (PCR, microscopy). We have developed a rapid, accurate and economical point-of-care viral diagnostic that is highly sensitive towards a bespoke common cold viral nucleotide sequence, so that individuals presenting with the symptoms of an RTI can be classified into those patients who have/ do not have the common cold. Clinical throat swabs samples are transferred to a lateral flow test strip, where aptamer-gold nanoparticle based sensing elements in combination with electronic components, such as optical sensors, easy to read displays, and custom designed embedded software interpret the results on behalf of the healthcare professional to indicate whether the patient is positive or negative for the common cold. Patients that exhibit a positive result for the presence of the rhinovirus are advised of therapy that will effectively manage their symptoms and

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to return if their condition exacerbate. Whereas, patients that are negative for rhinoviruses will be prescribed an appropriate antibiotic/course of therapy to treat their non-rhinoviral RTI. We envisage our technology will pave the way forward and complement existing strategies at overcoming antimicrobial resistance. Prof Thomas Krauss, University of York Physics and Electronics “Nanophotonic Antimicrobial Susceptibility Test” We are exploring nanophotonic methods based on guided mode resonances combined with electronic methods to assess bacterial susceptibility to antibiotics both at the level of individual bacteria and at the biofilm level. The goal is to develop a susceptibility test that can inform the clinical administration of antibiotics on a short (<30min) timescale, and to understand the penetration of antimicrobials through biofilms in order to understand recurring infections.

Dr Charlotte Bermingham, University of Bristol Physics, Social Community Medicine, Cellular and Molecular Medicine “Rapid detection of antimicrobial resistance” Rapid diagnostics have a key role to play in combatting antimicrobial resistance, as they will allow healthcare professionals to determine which antibiotics will be effective before prescribing. This will enable more targeted treatment, avoiding complications and long recovery times due to ineffective antibiotics, saving healthcare systems money and reducing the spread of resistance through reduced and more specific antibiotic prescription. We have developed a method to rapidly detect resistance to antibiotics based on a novel optical detection system, that does not rely on growth of the organisms. In proof of concept experiments we have demonstrated that we can detect resistance of E. coli to common antibiotics within 20 minutes. We now plan to characterise the response of more bacteria to a wide range of antibiotics in our system. Alongside scientific research, we have also been corresponding with healthcare professionals in various areas such as GPs, doctors and veterinarians to understand the problems faced when prescribing antibiotics and how our method could be incorporated into a device to for use in a point of care setting. This has been valuable for understanding the requirements such a technology would need to meet for adoption into the healthcare system and where it would make the biggest impact. Dr Sourav Ghosh, University of Nottingham Advanced Materials and Healthcare Technologies “Gold-Aptamer-Nanoconstructs Engineered to Diagnose the Common Cold” There is an immediate unmet need for a diagnostic technology that assists GPs and healthcare professionals when making point of care clinical prescribing decisions for respiratory tract infections (RTIs). Currently there is no easy to use low-cost desktop product that is able to stratify patients presenting with the symptoms of a RTI from viral or bacterial aetiology during the timeframe of typical GP-Patient consultation. As a result, antibiotics are overprescribed and have contributed to the rise of antimicrobial resistance, which is associated with both long-term medical and economic uncertainty. Existing solutions fall outside of the limited GP-Patient consultation timeframe (PCR, microscopy), require specialist skills to operate them (PCR, microscopy and ELISA) and are expensive (PCR, microscopy).

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We have developed a rapid, accurate and economical point-of-care viral diagnostic that is highly sensitive towards a bespoke common cold viral nucleotide sequence, so that individuals presenting with the symptoms of an RTI can be classified into those patients who have/ do not have the common cold. Clinical throat swabs samples are transferred to a lateral flow test strip, where aptamer-gold nanoparticle based sensing elements in combination with electronic components, such as optical sensors, easy to read displays, and custom designed embedded software interpret the results on behalf of the healthcare professional to indicate whether the patient is positive or negative for the common cold. Patients that exhibit a positive result for the presence of the rhinovirus are advised of therapy that will effectively manage their symptoms and to return if their condition exacerbate. Whereas, patients that are negative for rhinoviruses will be prescribed an appropriate antibiotic/course of therapy to treat their non-rhinoviral RTI. We envisage our technology will pave the way forward and complement existing strategies at overcoming antimicrobial resistance. Dr Geetha Srinivasan, Queen’s University Belfast Chemistry and Chemical Engineering, School of Pharmacy, Polymer Processing Research Centre “Novel Electronic Smart Devices for Healthcare Applications” Urinary tract infections associated with indwelling medical catheters are the most common type of healthcare-associated infections challenging the society. These infections are caused by bacterial or biofilm formation on the surface of the catheter. Patient discomfort through multiple invasions, clinical complications due to comorbidities caused by recurring infections, frequent consumption of antibiotics leading to antimicrobial resistance are all high impact and costly consequences as a result of this problem. In the current medical device market, antibiotic-coated and silver-coated urinary catheters are available to control catheter related infections. However, the antibiotics are prone to self-discharging spontaneously when in contact with body fluids, even when not needed. This leads to loss of active agent when needed at the onset of infection resulting in long term side-effects or occasionally, fatalities, due to antibacterial resistance. There is an urgent need to develop new methods of antibiotic delivery where the active pharmaceutical agent can be released at the target site directly and in a controlled manner. To achieve this we create novel functional materials and develop new methods to deliver antimicrobial agents. In this context, in our research team we fabricate electro-active materials that can sense the onset of infection and will be capable of delivering the antimicrobial agent directly at the infection site upon stimulation by a mild electrical pulse. In the state-of-the-art, oral drug delivery poses the danger of overdose or underdose, the latter can cause antimicrobial resistance. However, the concept of electrochemically controlled targeted drug delivery will be applicable in the control and treatment of infections in many types of medical implants - not limited to urinary catheters. The main challenge in achieving electrochemically controlled targeted drug delivery, is to develop electro-active and flexible polymer composites. Electronically conducting polymer composites formulated in our research will have a multifunctional characteristic both as a biosensor and drug release backbone. It also holds the potential to store electrical energy needed to release the drug molecules. These materials are “smart” as they can function upon activation by external stimulus. Smart electronic materials in our research are prepared using a novel class of solvents called ionic liquids. Ionic liquids are salts in a liquid form at room temperature that are non-toxic and environmentally friendly. We develop task specific ionic liquids and utilise them to develop smart polymer materials and test for bacterial sensing and antimicrobial activity upon activation by an electrical pulse. Ionic liquids play a multifunctional role as a solvent, as an electrolyte with API ingredient and as a plasticiser. The sensing and release mechanism of the catheter device will have the potential to be controlled remotely and be a user friendly device benefitting the patient, carer and clinical communities.

1. M. Lorenzo, B. Zhu and G. Srinivasan, Green Chem., 2016, 18, 3513-3517. 2. M. Lorenzo and G. Srinivasan manuscript entitled ‘Durable Flexible Supercapacitors

Using Ionic Liquid Technology’ - submitted

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Network Overviews 14:30-15:00 Chair: Prof Matt Keeling, Zeeman Institute Times Speaker Affiliation 14:30 Prof Tim Leighton Southampton

“Update on NAMRIP” 14:45 Dr Sandip Kumar Sheffield “SHAMROK brings together sciences, medicine, engineering and industry

to address AMR” 15:00 Dr Patrick SM Dunlop Ulster

“Northern Ireland Antimicrobial Resistance Network (NIAMR)” Network Overviews Abstracts Prof Tim Leighton, University of Southampton Network for AntiMicrobial Resistance and Infection Prevention (NAMRIP) NAMRIP (the Network for AntiMicrobial Resistance and Infection Prevention) was set up in 2015, and substantially supported by a networking grant of £868k from the EPSRC. Based at the university of Southampton, but with members and research partnerships across the globe, NAMRIP brings together engineers, chemists, microbiologists, environmental scientists, veterinary and human medics, clinicians who contribute to international and national antibiotic guidelines for specified conditions, experts in food, ethics and law, crucially networked with economists, geographers, health scientists and experts from other social science disciplines to provide a joined up approach to AMR and Infection Prevention. At the time, EPSRC funded 11 AMR networks across the UK. In the context of biofilms and AMR, NAMRIP approaches three broad phases of the problem: • Prevention of infection (e.g. prevent biofilms setting up as a consequence of bacteria breaching the skin barrier, either via the skin itself, or (more likely) through breaks in the skin at wounds, eyes, ears, mouth and digestive tract, nose, genito-urinary openings etc.); • Prompt identification of the microbe and effective treatment; • Reduction of the likelihood for resistance to develop and spread in wider world (e.g. sewage and agriculture systems; water supplies; local systems for delivering antibiotics etc.). NAMRIP achieves this through five areas of research: • Infection Prevention; • Behaviour in the Wider World; • Pharmacology and Therapeutics; • Sensing and diagnostics; • Clean water, sewage and waste. NAMRIP ensures understanding of, and sufficient momentum behind, its programme through very active Public Engagement and Public Policy operations. NAMRIP ensures there will be a suitably trained next-generation of researchers equipped to tackle the challenges of AMR through its Future Leaders programme. Our ECR-led Future Leader’s programme provides future multidisciplinary researchers who are passionate to translate their first-rate research to benefit society. In 18 months 13 ECRs have become Principle Investigators directly as a result of NAMRIPs Future Leaders programme. In the same time, NAMRIP has 3 patents granted, 10 patents pending, 3 licences with manufacturers, and 4 trademarks. This invests in sustainability by showing ECRs real translation from fundamental research, attracts

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industry funds, validates us for policymakers. We have a dozen partner bodies, mostly industry, who sponsor and collaborate in projects. Dr Sandip Kumar, University of Sheffield SHAMROK brings together sciences, medicine, engineering and industry to address AMR The Florey Institute’ at the University of Sheffield is focused on the study of the interaction between antibiotic resistant pathogens and the host. The University has also invested in the ‘Imagine: Imaging Life’ initiative which brings together super-resolution optical, cryo-electron and atomic force microscopy techniques with the aim of understanding living systems, and is working with microbiologists to understand bacteria and their interaction with host cells. At the other end of the spectrum, the Engineering and Medical Schools at Sheffield are applying novel engineering methods to heal wounds and kill bugs. Sheffield antimicrobial resistance network (SHAMROK) has aimed to bring together the University’s strengths. With this goal SHAMROK has funded pump-prime projects where microbiologists, clinicians, chemists, physicists, engineers and industry work together to address AMR. A few examples of funded projects that will be described in more detail are: 1. Development of Deformation based AMR detection for rapid diagnostics 2. Ultrasound as an antibiotic-free method to combat chronic intracellular infection 3. Correlative super-resolution and atomic force microscopy to understand bacterial cell wall synthesis The pump-prime projects have led to new collaborations, publications and successful grants. The preliminary data obtained from many of the pump-prime projects are being used to apply for grants to address AMR. Dr Patrick SM Dunlop, Ulster University Northern Ireland Antimicrobial Resistance Network (NIAMR) Patrick Dunlop is a Lecturer within the School of Engineering and a member of the Engineering Research Institute at Ulster University. His research interests focus on 1) the development of biological sensing technology, including rapid identification of organisms associated with antimicrobial resistance; 2) the design and application of nanomaterials for the disinfection of water/wastewater and the production of self-cleaning and self-disinfecting medical devices/surfaces. He is a member of the Judging Panel for the NESTA £10M Longitude Prize and Chair of the Northern Ireland Antimicrobial Resistance Network.

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Session 4: Biofilms, Infection Control & Modelling 15:15-16:45 Chair: Prof Elizabeth Wellington, School of Life Sciences Times Speaker Affiliation 15:15 Dr Esther Karunakaran Sheffield

“Chemical fingerprints of Acinetobacter sp. biofilms: a Raman microspectroscopy study”

15:30 Dr Michele Barbour Bristol “Preventing umbilical cord infection in low resource settings: a novel

biocide based topical material” 15:45 George Parry Warwick

“Infection in a Microfluidic Device” “Antimicrobial resistance and metabolite levels in slurry samples from dairy cattle in the UK”

16:00 Dr Robert Hyde Nottingham “Antimicrobial resistance and metabolite levels in slurry samples from

dairy cattle in the UK” 16:15 Prof Bill Graham Belfast

“Why plasmas/ionised gases have potential in managing Drug Resistive Infection

16:30 Prof Matt Keeling Warwick “Towards personalised empirical antibiotic guidance – a pilot study”

Session 4 Abstracts Dr Esther Karunakaran, University of Sheffield Chemical and Biologicall Engineering, Material Science Engineering “Chemical fingerprints of Acinetobacter sp. biofilms: a Raman microspectroscopy study” Extreme resistance to antimicrobials is a hallmark of chronic biofilm-based infections. No antimicrobial therapy can eradicate mature biofilms. Suppression of infection is possible with prolonged treatment and high doses of antimicrobials, which could result in evolution of antimicrobial resistance. The overall burden of biofilm infections is significant with 65% of all hospital-acquired infections related to biofilms contributing to a direct cost around £1 billion per year in the UK alone. In addition to conventional resistance mechanisms such as upregulation of multidrug efflux pumps and horizontal transfer of resistance genes, the recalcitrance of mature biofilms to antimicrobials is attributed to the extracellular polymeric substance (EPS) matrix - the dark matter - of the biofilms. A mechanistic understanding of the contribution of EPS to the structural stability and persistence of biofilms will allow the design of novel antimicrobial strategies to reduce the reliance on aggressive antimicrobial therapy and the risk of antimicrobial resistance evolution. Analytical techniques currently used to study EPS do not allow the resolution of spatial heterogeneity of EPS or rely on prior knowledge of EPS composition to choose appropriate labels. An unbiased approach to investigate the chemical fingerprints of biofilms is necessary. Therefore in this study we have assessed the feasibility of using Raman microspectroscopy to investigate the chemical makeup of biofilms of Acinetobacter sp., an emerging nosocomial pathogen. The

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results indicate that Raman microspectroscopy is an excellent non-destructive technique for an unbiased investigation of the chemical fingerprints of biofilms. Dr Michele Barbour, University of Bristol “Preventing umbilical cord infection in low resource settings: a novel biocide-based topical material” Umbilical cord infection (omphalitis) is a major threat to neonates in resource-poor settings, and can lead to systemic infection, sepsis, and death. Incidence data are sparse, but one study of 6904 neonates in Karachi, Pakistan, indicated that 1501 (21.7%) were diagnosed with omphalitis, with 9.3% of these exhibiting signs of sepsis. In 2014 the WHO issued a guideline recommending application of 4 % chlorhexidine (CHX) to the cord daily for the first week of life for home births in countries with high neonatal mortality. The CHX used is the highly soluble CHX digluconate (CHXdg), usually as a solution or gel. While this does reduce omphalitis, the drawback is the necessity for repeated applications which is difficult to achieve in remote or traditional communities or situations of conflict. What is urgently needed is a topical CHX formulation that can be applied to the cord only once immediately after birth, and that protects against infection for at least seven days without the need for further treatment. We report the investigation use of a novel antimicrobial technology to establish whether it might be of use in protecting neonates in resource-poor settings against omphalitis. Our technology, sustained efficacy chlorhexidine (SECHX), is a novel, patented material which releases the biocide chlorhexidine over an extended period. In this study we have gathered data to support its further development to create a product which only needs to be applied once to the umbilical cord, and which provides sustained protection against cord infection for 7 days. We report on the development and optimization of two prototype products: spray and emulsion cream delivery of SECHX. This approach could improve compliance with WHO recommendations for cord care and reduce deaths among the most vulnerable neonates. George Parry, University of Warwick Physics, Warwick Medical School “Infection in a Microfluidic Device” Microfluidics is an established technology based on soft-lithography. It combines the ability to do high-magnification microscopy with the possibility to design precise microenvironments whose physico-chemical properties can be dynamically controlled with high spatial and temporal precision. The microchannels are commonly made of polydimethylsyloxane (PDMS), a gas-permeable biocompatible elastomer with excellent optical properties. Ease of design/assembly and biocompatibility of PDMS have fostered the development of organ-on-chip devices in recent years: tissues grown within microfluidic devices that can be exposed to precise physical and chemical stimuli while their behaviour is studied at the single cell level. Effective interventions against antibiotic resistant S. aureus require an in-depth understanding of the infection process. S. aureus travels from the nasal or skin tissues to other organs via blood, causing serious invasive infections. Although the bacterium has been widely studied, we understand little about fundamental events like bacterial attachment, spreading and invasion during infection, particularly under flow conditions encountered in the host. S. aureus also forms complex communities or biofilms, and is able to enter and survive inside host cells. Examination of these infection-related processes within a microfluidic channel will provide new insights into staphylococcal pathogenesis. The proposed system enables us to study S. aureus-host interactions at single-cell level under nearly-physiological conditions.

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Dr Robert Hyde, University of Nottingham Veterinary medicine and science, Biosciences, Pharmacy, Engineering “Antimicrobial resistance and metabolite levels in slurry samples from dairy cattle in the UK” Antibiotic resistance within agriculture and the potential dissemination of resistant bacterial populations and antibiotics into the environment has attracted great concern. Cattle produce a large quantity of manure that is largely destined for agricultural application, which represents a route of AMR transfer into the environment both through direct transfer of resistant bacteria and through increased selection pressure in the soil environment through the transfer of antibiotic metabolites. Dried and separated manure has gaining some popularity in the UK as a cattle bedding substrate in the form of recycled manure solids (RMS), representing a potential for AMR levels to increase on cattle farms through this “closed loop” of slurry management. Slurry samples were collected from various stages along the slurry pathway from a UK dairy farm, milking 240 cows using 4 robot-milking units, on 2 separate occasions. Slurry samples were collected from all 4 adult cattle pens (Pens 1-4), the slurry-holding tank, liquid and solid fractions after separation, as well as from a solid manure sample stored for 30 days in environmental conditions. Antimicrobial drug usage levels from the previous 30 days were collected from farm medicine records. Samples were then cultured using TBX media to isolate non-type specific E.coli (NTSEC) and sensitivity testing was conducted to determine within-sample resistance prevalence levels to ampicillin, and subsequently concurrent resistance to tetracycline, kanamycin and cephotaxime. Determination of antibiotic metabolite levels is currently underway. Preliminary analysis demonstrates a pen level increase in ampicillin resistance, in one pen (pen 4, 1st round of sampling) which appears associated with increased usage of a systemic 1st generation cephalosporin. This increase in resistance appears correlated with an increase in ampicillin resistance for holding tank, post press samples, and stored samples, compared with subsequent results. Of pen 4 ampicillin resistant organisms, 86% (n=96) were concurrently resistant to cephotaxime, significantly higher than ampicillin resistant organisms recovered from the other 3 pens (17%, n=101, P<0.001). Preliminary results indicate an increase in ampicillin resistance levels in NTSEC in slurry recovered from group housed cattle, potentially in response to increased pen level antimicrobial usage, that appears to persist along the slurry-handling pathway. Perhaps more concerning is the significant increase in concurrent resistance to a 3rd generation cephalosporin (critically important antibiotic for human health) correlated with an increase in usage of a 1st generation cephalosporin (not currently classed as a critically important antibiotic in veterinary medicine). Prof Bill Graham, Queen’s University Belfast Pharmacy, Centre for Plasma Physics “Why plasmas/ionised gases have potential in managing Drug Resistive Infection” The plasma is an ionised gas where some or all of the atomic constituents are electrically charged i.e. the gas contains ions (positively charged atoms or molecules) and electrons (negatively charged). The production of these charged particles requires an input of energy, in most cases through the application of an electric field to drive electrons at energies that will create ionising collisions with the constituent atoms or molecules. A by-product of these electron collisions will be excitation of both bound electrons, hence light emission. There will also be molecular rotational and vibrational excitation up to the point where the molecules dissociate, hence creating new chemical pathways. This plasma-induced chemistry has been recognised since the first electrical production of ozone and the synergy of plasma physics and chemistry is still the primary method for etching the nano scale features in silicon microchip production. However these plasma systems either also heat the gas or require low pressures. In the last decade plasma devices capable of producing cold gas (~ 60 0C), reactive, plasmas at atmospheric pressure were developed and this has led to the rapid growth of interest in plasma applications in areas such as

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medicine, food and agriculture. Sources typically used in the QUB antimicrobial programme will be described and the underpinning broad plasma science discussed. The task of understanding the science in these applications is further exacerbated by the interactions of the active plasma with the media containing the active agent. A sample of the wide variety of diagnostic tools and computer-based simulations that are currently being deployed to tackle these issues will be presented. Finally the recent developments in “plasma activated water” will be briefly described. The results from the various aspects of the QUB programme will be presented at a number of talks throughout the meeting. Dr Ben Collyer, University of Warwick Zeeman Institute, Heart of England NHS Trust “Towards personalised empirical antibiotic guidance – a pilot study” Every hospital should produce empirical antibiotic treatment guidelines. These indicate the initial agent that should be given for a specific condition. Infection specialists strike a balance between narrow spectrum (which might fail to be effective) and broad-spectrum agents (which risk the selection of resistant organisms). They take a number of factors into consideration: eg. the syndrome requiring treatment, patient’s risk factors for acquiring a resistant organism. Good guidelines are the cornerstone of antibiotic stewardship and recommended by NICE. However – by their very nature they have to be fairly cautious, tending towards broader agents where there may be doubt. This is of concern. The presence of an antibiotic in a host or ecosystem is associated with the emergence of resistant strains. Studies in primary care – facilitated by many years of electronic prescribing systems – have clearly demonstrated an association between antibiotic use and the development of resistance at the patient level. There is a dearth of such patient-level studies conducted within hospitals. The last few years have seen NHS hospitals implement much more ambitious clinical information technology systems. Companies such as Google are partnering with the NHS to develop intelligent systems that will analyse this information and recognise patients at risk of deterioration. Another area with tremendous potential for development is that of empirical antibiotic choice: by leveraging the patient level data available within a hospital it will be possible to assess each individual patient’s risk for resistant infection and produce a recommendation for the most appropriate empirical treatment for a specific patient with a specific condition on a specific admission. This has tremendous potential to reduce the use of broad-spectrum agents and the associated risks to patient and public health. Such intelligent systems have not been previously described. This project aims to demonstrate that such a system is possible – firstly by demonstrating that it is possible to integrate and analyse retrospective data to identify factors associated with resistant infection and poor outcome; secondly by using this information to develop algorithms to guide a personalised antibiotic recommendation based upon a specific patient’s risk factors.

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Exhibitors

Microbiology Society The Microbiology Society is a membership organisation for scientists who work in all areas of microbiology. It is the largest learned microbiological society in Europe with a worldwide membership based in universities, industry, hospitals, research institutes and schools. Learned Societies Partnership on Antimicrobial Resistance (LeSPAR) LeSPAR is a partnership of 7 learned societies representing 75,000 scientists has come together to lead the fight against antimicrobial resistance. LeSPAR aims to provide a single, unified voice and mobilise the UK’s collective research community in order to enhance understanding and knowledge sharing between academia, industry, and clinicians. The group is focused on taking action, championing best practice and raising awareness of the global challenge of antimicrobial resistance. Membership: Biochemical Society, British Society for Antimicrobial Chemotherapy, British Pharmacological Society, Royal Society of Chemistry, Society for Applied Microbiology, Microbiology Society, Royal Society of Biology EPSRC The EPSRC is the main UK funding agency for training and research in engineering and physical sciences. As part of the Cross Council Initiative in Antimicrobial Resistance (AMR) EPSRC launched a call in September 2014 to engage engineering and physical sciences (EPS) researchers with the AMR challenge and to develop networks within their institutions focussed on the four multidisciplinary themes identified in the AMR Cross Council Initiative. These networks support people to build capacity and understanding which could lead to future research proposals. MRC The MRC works to improve the health of people in the UK - and around the world - by supporting excellent science, and training the very best scientists. The MRC funds a wide range of research in AMR from laboratory to bedside. The MRC has been working with the seven UK research councils, along with other UK funders, in a cross-council initiative to develop collaborative approaches across research disciplines and to identify a number of research opportunities and challenges in tackling the rise in AMR. Longitude Prize The Longitude Prize is a five-year challenge with a £10 million prize fund. It will reward a competitor that can develop a transformative, accurate, affordable and rapid point–of–care diagnostic test that is easy to use, anywhere in the world and will conserve antibiotics for future generations. The Discovery Awards programme, launched on 16th May 2016 and funded by GSK and BIRAC, are seed grants of up to £25,000 each to support existing teams to further develop ideas, and to encourage new innovators from a range of disciplines, sectors and countries to get involved. Antibiotic Action Antibiotic Action is a global public awareness initiative to inform everyone about drug resistance. We work with a wide variety of people, including professionals as well as the general public. We urge everyone to use existing antibiotics wisely and we promote the importance of infection prevention and control. However, we desperately need new treatments for infections and we recommend enhancing global efforts to discover these treatments.

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The ‘Bridging the Gaps’ Network Principal Investigator

Holding Organisation Grant Title

Pitt, Professor AR Aston University

Aston Multidisciplinary Research for Antimicrobial Resistance: The AMR4AMR project

Smith, Professor MCM University of York

TARGeTED: Tackling Antimicrobial Resistance through Goal-orientated Thinking in the EPS Disciplines

Malik, Dr DJ Loughborough University

Tackling Antimicrobial Resistance: An Interdisciplinary Approach

Leighton, Professor T

University of Southampton

NAMRIP - Network for Antimicrobial Resistance and Infection Prevention

Keeling, Professor M

University of Warwick

Cross-scale prediction of Antimicrobial Resistance: from molecules to populations. (INTEGRATE AMR)

Hobbs, Professor J

University of Sheffield

Sheffield antimicrobial resistance network - SHAMROK

Mulholland, Professor AJ

University of Bristol

BristolBridge: Bridging the Gaps between the Engineering and Physical Sciences and Antimicrobial Resistance

King, Professor J

University of Nottingham

Bridging the Gaps: Systems-level approaches to antimicrobial resistance

Dorey, Professor RA

University of Surrey

Novel Strategies to Detect and Mitigate the Emergence of AMR in Zoonotic Pathogens

Toumazou, Professor C

Imperial College London

Engineering, Physical, Natural Sciences and Medicine Bridging Research in Antimicrobial resistance: Collaboration and Exchange (EMBRACE)

Bell, Professor SEJ

Queen's University of Belfast

Building the Queen's University of Belfast AMR Network (QUBAN)

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Aston: Aston Multidisciplinary Research for Antimicrobial Resistance: The AMR4AMR project

PI: Prof Andrew Pitt (School of Health and Life Sciences) Aston Multidisciplinary Research for Antimicrobial Resistance, the AMR4AMR project, is generating an active and vibrant research environment that brings together researchers from across Aston to focus holistically on the problem of antimicrobial drug resistance to find new and innovative solutions. Antimicrobial resistance, the ability of microorganisms to overcome almost all of the antimicrobial treatments that we currently have, has been identified as one of the main challenges facing the 21st century. Unless we find new approaches to deal with these bugs, it might not be long before we will find ourselves in a situation similar to times before the development of the penicillins, where simple infections turn out to have deadly consequences. Through the generation of an environment that is actively supporting an interdisciplinary approach, new and innovative science and engineering and better practices are being developed; these are providing the foundation for ensuring we stay one step ahead of the superbugs.

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York: TARGeTED: Tackling Antimicrobial Resistance through Goal-orientated Thinking in the EPS Disciplines W: https://www.york.ac.uk/staff/research/research-development/targeted-amr-project T:@UoYTargeted The University of York TARGeTED Community is developing new interdisciplinary collaborations and innovative approaches to tackle the AMR challenge. Inspiring goal-orientated research we are bringing together staff from across departments to develop: Novel tools for understanding and controlling bacterial behaviour Novel biosensors and diagnostics Our objectives A clear and shared understanding of the elements of the AMR Challenge that University of York is best placed to address A culture of engagement with ‘goal-orientated’ thinking between Engineering, Physical, Biological and Social Scientists Active and developing collaborations to enable knowledge exchange Proof-of-principle research to test the validity of our proposed solutions to AMR problems Governance structure Chair Professor Maggie Smith (Biology) Steering Group Professor Martin Bees (Mathematics), Dr Steve Johnson (Electronics), Professor Thomas Krauss (Physics), Professor Susan Stepney (Computer Science), Professor Tony Wilkinson (Chemistry), Emma Brown (Research & Enterprise Office), Dr Rachel Curwen (Research & Enterprise Office)

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Loughborough: Tackling Antimicrobial Resistance: An Interdisciplinary Approach Loughborough team: PrincipaI Investigator – Dr. Danish Malik (Chemical Engineering, CE); Diagnostics Lead – Dr Sourav Ghosh (Mechanical Engineering, ME), Global Health Lead – Dr Emily Rousham (School of Sport, Exercise and Health Sciences, SSEHS); Mathematical Modelling Lead – Dr John Ward (Mathematical Sciences); Chemistry Lead – Dr Marc Kimber (Chemistry); Project Coordinator – Dr Ilya Sokolov (Chemical Engineering). Workshop and Networking events: Official launch followed by four international workshops focusing on diagnostics, urinary tract infections, wounds and biofilms. Funded interdisciplinary pump-priming projects Research Focus Area 1: Diagnostics • A novel electrochemical nonlinear acoustic method for direct detection of bacterial infection – Dr. Sourav Ghosh (PI, ME) • Microfluidic bioparticle manipulation for ultrasensitive and rapid diagnostics for AMR – Dr. Guido Bolognesi (PI, CE) • To characterize the volatile metabolites for bio-profiling infecting organisms in chronic wounds in order to evaluate their potential for use as biomarkers of AMR and biofilm infection – Dr. Elizabeth Ratcliffe (PI, CE) • A novel platform for rapid and direct detection of diarrheagenic pathogen combining nonlinear acoustic technique with molecular imprinted polymer – Dr. Sourav Ghosh (PI, ME) • Rapid detection of E. coli in fluoropolymer microcapillary films – Dr. Nuno Reis (CE) • To characterize the volatile metabolites produced by strains of Pseudomonas aeruginosa in order to evaluate their potential for use as biomarkers of VAP in non-invasive breath analysis – Dr. Martin Lindley (PI, SSEHS) • Direct isolation and detection of bacteria from whole blood for rapid sepsis diagnostics – Dr. Sourav Ghosh (PI, ME) Research Focus Area 2: Bioprocessing and targeted delivery of antimicrobials • Encapsulation of bacteriophages and bacteriocins using membrane emulsification for controlled release applications – Dr. Danish Malik (PI, CE) • Formulating bacteriophage based antibiotics using dry granulation and direct compression tableting technology for gastrointestinal applications – Dr. Mark Leaper (PI, CE) • Formulation and stabilisation of novel antibiotics in foams and porous substrates – Dr. Anna Trybala (PI, CE) • Spray drying of bacteriophages – Dr. Andrew Stapley (PI, CE) Research Focus Area 3: Smart Materials • Development of new antibacterial polymer coatings to prevent biofilm formation - Dr Ignacio Martin-Fabiani (PI, Materials) • Evaluating the effect of a photocatalytic antimicrobial coatings (PAC) on healthcare surfaces – Prof. Gianluca Li Puma (CE) • Antimicrobial growth on maxillofacial prostheses – Prof. Richard Bibb (PI, School of Design) • Polymeric coatings for easy clean surfaces – Dr. Simon Martin (PI, Materials) Research Focus Area 4: Urinary Tract Infections • Reducing antibiotic resistance, urinary tract infections and asymptomatic bacteriuria in kidney transplant recipients: effects of an exercise intervention – Dr. Nicolette Bishop (PI, SSEHS) • Reducing misdiagnosis and antibiotic prescribing practices in hospitals: a proof of principle study of diagnosis, management and treatment of urinary tract infections in adults over 65 years – Dr. Emily Rousham (PI, SSEHS) • Microbiology of asymptomatic bacteriuria in elderly patients to identify novel diagnostic biomarkers – Dr. Emily Rousham (PI, CE)

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Southampton: NAMRIP - Network for Antimicrobial Resistance and Infection Prevention PI: Prof Tim Leighton (Engineering) We combine world class research with an interdisciplinary approach in combatting the increasing resistance that microbes display to countermeasures like antibiotics Our Goals are to • integrate responses, through research excellence across our faculties • enable engineers, physical scientists, clinicians and social scientists to work

together • find ways through these means, to bring antimicrobial resistance under control

and attack this problem by preventing infection The AMR threat is being tackled by researchers across the UK Governance Structure Chair: Professor Tim Leighton Steering Group: Professor Robert Eason, Professor William Keevil, Professor Robert Read, Professor Robert Wood, Dr Yuan Huang, Dr Rob Howlin, Dr Emma Roe, Dr David Voegeli, Dr Clint Styles, Professor George Attard, Professor Jeremy Frey, Professor Mandy Fader, Dr Steve Dorney If you are interested in joining NAMRIP contact either: the Interdisciplinary Research Coordinator for this group, Frances Clarke or the NAMRA grant coordinator for the group, Yvonne Richardson

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Warwick: Cross Scale Prediction of Antimicrobial Resistance – from molecules to populations (INTEGRATE AMR) The Power of Quantitative Thinking The quantitative and predictive skills of EPSRC remit sciences are key to creating a step-change in the study of AMR in terms of: understanding mechanisms of AMR, prediction of potential novel antibiotic targets and methods to contain and control AMR spread. Strategy: Our research programme is designed to integrate antimicrobial resistance expertise across disciplines and to foster a collaborative environment for innovative projects. Pump priming projects: warwick.ac.uk/WAMIC/INTEGRATE/pumpriming/ Lead PI: Prof Matt Keeling (Mathematics and Life Sciences) Management Committee: Prof Deirdre Hollingsworth (Mathematics and Life Sciences), Dr James Covington (Engineering), Dr Neil Evans (Engineering), Prof Matthew Turner (Physics), Prof Stephen Brown (Physics), Prof Greg Challis (Chemistry), Prof Matt Gibson (Chemistry and Medicine), Dr Nick Waterfield (Medicine), Prof David Roper (Life Sciences), Prof Chris Dowson (Life Sciences)

Project Manager: Dr Chandrika Nair Warwick AMR community: 100+ researchers across disciplines and partners in public health and industry

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Sheffield: Sheffield antimicrobial resistance network – SHAMROK The Sheffield Antimicrobial Resistance Network (SHAMROK) aims to enable new research and translational opportunities for tackling the growing threat of antimicrobial resistance. It is targeted on two broad areas:

• The development of physical and physico-chemical tools for understanding bacteriology and the host response.

• The development of new surfaces, dressings, and tissue engineering related approaches for preventing infections and improved drug delivery strategies for antimicrobials.

SHAMROK aims to develop a framework to nurture and develop new research opportunities to augment those already in place as part of our Imagine: Imaging Life (www.imagine-imaginglife.com) initiative and The Florey Institute (www.floreyinstitute.com). Team: Prof Jamie Hobbs - Network Lead (Physics and Astronomy) Christina Metcalfe - Network Manager Dr Sandip Kumar - Scientific Experimental Officer Co-investigators: Prof Simon Foster (Molecular Biology and Biotechnology) Prof Sheila MacNeil (Materials Engineering) Prof David Dockrell (Infection and Immunity) Dr Simon Jones (Chemistry) Funded interdisciplinary projects list:

1. Development of a Cerium-Containing Electrospun Antibacterial Wound Dressing. 2. Understanding the ingestion of pathogens as route to improved immune response

and antimicrobial therapy. 3. Biocidal Structured Surfaces. 4. Engineering Novel Antimicrobial Peptide Surfaces. 5. Feasibility of using non-invasive Raman Imaging and computational modelling to

resolve three-dimensional EPS distribution in biofilms. 6. Mass spectrometry analysis of rRNA modifications in S. pneumoniae and S.

aureus. 7. Development of boronic acid derivatives as novel antimicrobials targeting serine

beta-lactamases and Penicillin-Binding Proteins. 8. Ultrasound as an antibiotic-free method to combat chronic intracellular infection. 9. Immobilised novel singlet oxygen photosensitisers for antimicrobial water

treatment by sunlight. 10. Walking on water: the motility of pathogenic bacteria during initial stages of lung

Infection. 11. Synthetic bacterial decoys to inhibit microbial infection.

Our network’s overarching aim is to limit the reliance on existing antimicrobial strategies through replacement with new antimicrobials, novel antimicrobial delivery, immune based strategies and tissue engineering approaches to prevent microbial colonization. W: www.shamrok.org T: @SheffieldAMR

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Bristol: BristolBridge - Bridging the Gaps between the Engineering and Physical Sciences and Antimicrobial Resistance

www.bristol.ac.uk/bristolbridge/ BristolBridge team: Lead and PI – Prof Adrian Muholland (Chemistry); Deputy Chair – Prof Jeremy Tavaré, Director, Elizabeth Blackwell Institute for Health Research; Impact Lead – Dr Matthew Avison (Cellular and Mol. Med); Research strand leads: Strand 1: Novel antimicrobials, assays and diagnostics. Dr Jim Spencer (Cellular & Mol. Med) and Dr Annela Seddon (Physics). Strand 2: Antimicrobial materials and devices. Dr Michele Barbour (Oral and Dental Sciences) and Dr Sabine Hauert (Engineering Maths and Bristol Robotics Lab) Strand 3: AMR surveillance and interventions. Dr Katy Turner (Vet. Sciences & Social and Community Med) and Dr Martin Homer (Engineering Maths). Manager & Research Facilitator – Dr Claire Spreadbury (Chemistry). Networking events: Research strand brainstorms; Official launch; Research seminars; World Café; Inaugural Conference; Workshops - Diagnostics (with the Institute of BioSensing Technology), Data Science Meets AMR (with the Jean Golding Institute for data-intensive research); SW Schools Conference on Antimicrobial Resistance Science; Bristol Tackles Global Challenges week (with the Bristol Synthetic Biology Research Centre); Bridging the Gaps between Academia, Translation & Commercialisation (with Enterprise Europe Network SW); Annual Conference & Industry Day: Building Partnerships to Tackle the Global Challenge of AMR. Achievements: BristolBridge has built a Network of over 200 investigators from 4/6 Faculties, partners in the GW4 and LMICs; Nucleated new interdisciplinary research collaborations & funded 18 projects (4 have follow-on funding); Trained 30 EPS postdocs/PhD students in microbiology techniques; Industrial partnerships with SMEs: Outreach activities for members of the public & school children, consultants for Surgeon X, BristolBridge AMR CrossFire; Leveraged further funding for activities through EPSRC IS, EPSRC GCRF IS, GW4 and URC International Strategic Fund; BristolBridge-funded PIs & Co-Is have received cross-council AMR Theme 2, 3 and 4 & Newton Fund awards. Funded interdisciplinary pump-priming projects (including PI and host School) 1.Early phase development of a primary care device to detect rapidly antibiotic resistance in common bacteria (Antognozzi, Physics) 2.Identifying single bacteria through their acoustic Raman signatures (Gersen, Physics)

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3. Investigating electrostatic capture of bacteria using the electrochemical quartz crystal microbalance (Shwarzacher, Physics) 4. Devices for detecting AMR in LMICs; on-chip magnetic separation, concentration & detection of bacteria (Seddon, Physics) 5. Evaluation of nano-mechanical cantilever-based biosensors as a novel, rapid approach to detect antifungal resistance in pathogenic Candida species (Miles, Physics) 6. Rapid identification of UTI bacteria & their antibiotic susceptibility using volatile profile sensing technology (Avison/Ratcliffe, Cellular & Mol. Med/UWE) 7. Novel ways of improving antibiotic delivery to promote the direct killing of Neisseria gonorrhoeae (Hill, Cellular & Mol. Med) 8. A systems-based platform for the production of novel antibiotics (Foster, Biological Sciences) 9. Assay development for bacterial phosphoethanolamine transferases that confer resistance to last resort antibiotics (Pringle, Chemistry) 10. Identifying & characterising inhibitors of essential enzymes as routes to new anti-tuberculosis therapies (Mulholland, Chemistry) 11. Biomimetic antimicrobial surfaces to combat antimicrobial resistant infection (Su, Oral & Dental Sciences) 12. Developing novel biocompatible and antimicrobial coatings for orthopaedic implants (Tarlton, Veterinary Sciences) 13. A sustained delivery chlorhexidine gel for prevention of umbilical cord infection in developing countries (Barbour, Oral & Dental Sciences) 14. Towards a flexible and multi-use databank for veterinary AMR research (Reyher, Veterinary Sciences) 15. Mathematical modelling of the impact of novel AMR diagnostics for N. gonorrhoeae (Turner, Social & Comm. Med) 16. Developing strategies to minimise AMR in territorial wildlife population (Giuggioli, Eng. Maths) 17. Investigating AMR gene transfer in the aerosol phase (Reid, Chemistry) 18 Installation and development of a collaborative virtual reality laboratory for AMR outreach (Glowacki, Chemistry)

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Nottingham: Bridging the Gaps: Systems-level approaches to antimicrobial resistance PI: John King (Mathematical Sciences) W: http://www.nottingham.ac.uk/research/groups/bridging/ T:@BridgingtheGaps

Bridging the Gaps aim to create and support cross-disciplinary networks of researchers who will develop novel systems-level approaches to antimicrobial resistance. We will deliver a programme of activities to promote new collaborations between engineering, the physical sciences and the biological sciences, with additional scope to include collaborations with non-EPS researchers such as social scientists whenever this is of benefit to EPS research. Researchers will explore diverse subjects such as AMR in the environment, water supply, agriculture, drug discovery and delivery, GP prescribing, Point of Care testing and AMR data discovery tools. We promote collaborations with events focused on addressing AMR challenges. These include industry Challenge days, sandpit events and networking events. Challenge days bring researchers together with industrial partners and clinicians to align research developments with the needs of potential end users and to research specific questions with immediate impacts. Sandpits support researcher groups to identify specific research problems and to find solutions to those problems in novel and unpredictable ways. Researchers will also benefit from the expertise of leading AMR experts in our Visiting Scholar seminar series. Pump prime funding is available to cross-disciplinary research groups via direct application to the Bridging the Gaps Award fund and via Sandpit prizes. Bridging the Gaps supports the new generation of research scientists by offering AMR undergraduate research projects and by organising AMR clubs and events for PhD students and postdoctoral researchers. Bridging the Gaps is directed by its own Strategy group, formed of ten researchers from across The University of Nottingham.

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Surrey: Novel Strategies to Detect and Mitigate the Emergence of AMR in Zoonotic Pathogens CHAIR (Collaborative Hub for Advancing Interdisciplinary Research) PI: Robert Dorey (Mechanical Engineering Sciences) Roberto La Ragione (Veterinary School) Johnjoe McFadden (Bioscience) Maxim Shkunov (Electrical and Electronic Engineering) (PI until November 2016: Richard Curry (EE)) Focus on veterinary science, detection and data. Involvement in project from veterinary science, biosciences, mathematics, computing, electrical and chemical engineering, chemistry, physics and NPL. CHAIR activities: interdisciplinary seminar series with internal and external speakers, 2 funding sandpits, outreach events Projects funded: Project Title Project lead Other disciplines involved Antifouling Coatings to Prevent Biofilm Formation

Dr Peter Roth Chemistry

Physics, Bioscience,Vet School,NPL

Towards selective detection of AMR bacteria with a disposable electrical sensor

Dr Maxim Shkunov ATI/Electrical Engineering

Vet School, Chemistry

Putting your finger on the problem - detecting antibiotics and their metabolites in fingerprints

Dr Melanie Bailey Chemistry

Vet School, NPL, NHS

Towards low cost very rapid diagnostics

Dr Dan Horton Vet School

Electronic Engineering, Vet School

AMR data in time and space; Animal-Human-Environment ESBL transfers

Dr Ingrid den Uijl Vet School/Prof Gianne Derks Maths

Vet School, Centre for Environmental Strategy, Centre for Health Care Management and Policy

Understanding the pharmacokinetics of antibiotic implants for veterinary applications

Dr Tao Chen Chemical and Process Engineering

Vet School, Chemical and Process Engineering

Modelling in mycobacterial persistence Dr Lillian Tang Computer Science

Bioscience

Surface printing to investigate drug effects on real surfaces

Dr Suzie Hingley-Wilson Bioscience

Vet School, Mechanical Engineering and NPL

Measurement of drugs and metabolites in mycobacterial cells

Prof Johnjoe McFadden Bioscience

Chemistry

CHAIR

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Imperial: Engineering, Physical, Natural Sciences and Medicine Bridging Research in Antimicrobial resistance: Collaboration and Exchange (EMBRACE)

The purpose of EMBRACE is to bridge the gaps between Engineering, Physical and Natural Sciences and Medicine within Imperial College to challenge the current threat of antimicrobial resistance. The programme is principally designed to develop a cohort of interdisciplinary research fellows who will develop a unique set of hybrid research skills, a positive attitude to multidisciplinary research and the ability to communicate across traditional academic boundaries. Facilitating cross-disciplinary research in AMR at Imperial College, EMBRACE supports five pump-priming projects and one sandpit award. All the pump-priming teams have the participation of at least one EMBRACE Fellow, and are truly multidisciplinary, not just cross department but cross faculty and some involve researchers who have not previously applied their work to the field of AMR. The aim is to support successful proof of concept studies that foster multidisciplinary consortium formation with mid to long-term collaboration, generating pilot data that will lead to successful application for larger grants. In addition to this, EMBRACE has conducted a range of activities including developing the AMR virtual network, conferences and seminars to generate awareness and promote collaboration. Principal and co-investigators: Professor Christofer Toumazou, Winston Wong Chair of Biomedical Circuits and Regius Professor of Engineering, Chair in Biomedical Circuit Design. Professor Alison Holmes, Professor of Infectious Diseases at Imperial College and the Director of Infection Prevention and Control (DIPC) and Associate Medical Director for Imperial College Healthcare NHS Trust. Professor Alan Armstrong, Head of Department of Chemistry. Dr Pantelis Georgiou, Reader at Imperial College London within the Department of Electrical and Electronic Engineering. The EMBRACE Fellows: Dr Pau Herrero Viñas is currently a Research Fellow (EMBRACE) within the Centre for Bio-inspired Technology at Imperial College London. His main focus of research in AMR is on developing point-of-care decision support systems to optimize antimicrobial prescribing in intensive and secondary care settings. Dr Maryam Modarai is a Research Fellow (EMBRACE) within the department of Medicine at Imperial College London. Dr Dominic Affron Research Associate in Organic Synthesis/Chemical Biology at Imperial College London. Dr Lindsay Evans is a former EMBRACE Fellow, she currently holds a Wellcome Trust: Pathfinder Award EMBRACE pump priming projects and sandpit award: 1. Rapid Evaporative Ionisation Mass Spectrometry for Early detection of Antimicrobial Resistance (Professor Zoltan Takats, Surgery and Cancer) 2. Targeting quadruplex-DNA in the promoters of genes associated to antibacterial resistance (Professor Ramon Vilar, Chemistry)

http://www.imperial.ac.uk/arc/embrace/

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3. Antimicrobial resistance in gut communities (Dr Caroline Colijn, Mathematics) 4. LIPID-MINDS: Lipid Mapping to Identify Novel Drug Solutions (Dr Gerald Larrouy-Maumus, Life Sciences) 5. Real-time Enhanced Antimicrobial ConTroller (REACT) (Dr Timothy M Rawson, NIHR HPRU HCAI & AMR) 6. Promoting Immune Clearance of Bacterial Pathogens (Dr Andrew Edwards, Bacteriology) EMBRACE seminars: 1. Dr Gabriel Birgand, Research Associate and ARC Fellow, Dep Medicine, "Measures to control the spread of Multi-drug resistant organisms in hospitals: what are the current problematics?”. 2. Dr Enrique Castro, Lead Research Nurse (CIPM), Dept. of Medicine “Do Android (phones) dream of health games and apps? Exploring e/g-health interventions in patient safety”. 3. Dr Nickolas Croucher, Faculty of Medicine, School of Public Health, “Using whole genome sequencing to investigate the national and international spread of multidrug-resistant S. pneumoniae lineages” and Dr Elita Jauneikaite, Research Associate at the NIHR “Using whole genome sequencing to investigate healthcare associated infections and antimicrobial resistance”. 4. Prof Ramesh Wigneshweraraj, Professor of Molecular Microbiology, "Phage-inspired solutions to combat antibacterial resistance?” 5. Dr Nick Voulvoulis, Environmental Technology, “Antibiotics in the environment, implications for Antibiotic-Resistance”. 6. Jesus Rodriguez Manzano, Research Fellow, Electrical Engineering, "Towards rapid point-of-care diagnostics for infectious diseases and antimicrobial resistance". 7. Caroline Colijn, Mathematics, “Bacterial Olympics: Competition and resistance” and Professor Alex Cook Prof Alasdair Cook Head of Department of Veterinary Epidemiology & Public Health. 8. Dr Tim Rawson, "Enhanced, Personalised, and Integrated Care for Infection Management at the Point-of-Care” 9. Dr Avinash Shenoy, “Caspase targets in host immunity to infection” and Professor Jackie Hunter, “AI and Biomedicine: Culture clash or marriage made in heaven” and Richard Compton, “Nanopore Sequencing, with a focus on Infectious Diseases”

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Belfast: Building the Queen's University of Belfast AMR Network (QUBAN) QUBAN aims to promote interdisciplinary collaborations between researchers in the Schools of Biology and Medicine, Dentistry & Biomedical Sciences, who work on antimicrobial resistance with researchers from Engineering, Physical Sciences and Pharmacy (EPSP) who have access to novel approaches and expertise in techniques that could be exploited in AMR research. The activities of QUBAN are aimed at building the network itself, which will allow new ideas to be created, and then supporting early proof-of-principle studies to bring the ideas to the point where they can justify further support through conventional funding mechanisms. The QUBAN Network Investigators: Prof Steven Bell (CCE) Prof Jose Bengoechea (MDBS) Prof Colin McCoy (Pharmacy) Prof Stuart Elborn (MDBS) Prof W. Graham (Mathematic and Physics) Professor Fraser Buchanan (School of Mechanical and Aerospace Engineering) Prof Brendan Gilmore (Pharmacy) Steering Committee: Prof James McElnay (PVC for Research, QUB) Prof Rafael Canton (University Hospital Ramon y Cajal, Spain) Prof Duncan Graham (Centre for Molecular Nanometrology, Strathclyde) Prof Chris Hardacre (Head of School, Chemistry and Chemical Engineering, QUB)

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Further Information and Updates will be

posted on the Symposium Website:

warwick.ac.uk/WAMIC/symposium