Tackling AMR – A Cross Council Initiative
Antimicrobial resistance (AMR), especially resistance to antibiotics, is a growing global problem. We are facing a rise in the number of bacteria becoming resistant to existing antibiotics without an increase in new antibiotics or new treatments. It is clear that an interdisciplinary approach is needed to tackle these challenges and make a step change in addressing antimicrobial resistance. The AMR Funders Forum, has identified key themes to target current and future investments. These themes will foster collaboration between diverse disciplines, share information across the public and private sectors, allow access to tools, compound libraries, datasets and screens to acquire new insights into the emergence and spread of antibiotic resistant bacteria, the evolution of resistance and to drive the discovery of new diagnostic, preventative and therapeutic strategies for bacterial infections particularly antibiotic resistant strains.
The current focus of this initiative is on resistant bacteria of humans and animals but we acknowledge antimicrobial issues in other classes of pathogens and other target species such as plants, which will not be addressed through this initiative.
A thematic approach
Despite a strong basic bacteriology portfolio across the UK, funded through a number of sources, there are still many gaps in our understanding of the molecular and cellular biology of bacterial resistance, especially how bacteria evolve, acquire and transmit antibiotic resistance and how they adapt to life in human and animal hosts.
A deeper understanding of resistance forming bacteria from genomics, through to cellular and host pathogen interactions will unveil new potential targets for antibacterials, new paradigms for diagnostics and surveillance and greater insights into fundamental mechanisms of resistance development. It will also facilitate the development of new models, both in vitro and in vivo, as well as functional screens for the evolution of resistance.
Working across disciplines, the identification of new “druggable” antibacterial targets through the application of structural, systems and synthetic biology will be accelerated. Bioinformatics, computational biology and mathematical modelling will facilitate systems-level approaches to better understand resistance mechanisms, their evolution and spread in human- and animal- bacterial pathogens. Population, single cell and molecular level understanding of resistance mechanisms and antibacterial mechanisms of action will be investigated using advanced structural and imaging approaches through fostering links between the biological and physical sciences.
This theme is expected to provide the basic knowledge to underpin many of the other activities and will aim to:
- provide better understanding of resistant bacteria in the host context;
- identify new targets for novel antibacterials;
- define better ways of predicting and influencing the acquisition and evolution of resistance; and
- uncover new markers for diagnosing bacterial infection, virulence and resistance.
- Sharon Peacock (Chair) – University of Cambridge
- Maggie Smith (Deputy Chair) – University of York
- Antoine Andremont - University of Paris-Diderot Medical School, France
- Boyan Bonev – University of Nottingham
- Gordon Brown – University of Aberdeen (Innovation grants only)
- Mervyn Singer- University College London
- Martin Buck – Imperial College London
- Sarah Coulthurst – University of Dundee (Innovation grants only)
- Chris Dowson – University of Warwick (Innovation grants only)
- Anders Folkesson – Technical University of Denmark
- Gad Frankel – Imperial College London
- Stephen Gillespie – University of St Andrews (Collaboration Grants only)
- Julian Ketley – University of Leicester (Innovation grants only)
- Vassilis Koronakis – University of Cambridge (Collaboration Grants only)
- James O’Gara – National University of Ireland Galway (Innovation grants only)
- Malcolm Page – Basilea Pharmaceutica
- Sheila Patrick – Queen’s University of Belfast
- Laura Piddock – University of Birmingham (Innovation grants only)
- Robert Read – University of Southampton
- Daniel Ritz – Actelion Pharmaceuticals
- Andrew Rycroft – The Royal Veterinary College
- Thamarai Schneiders – University of Edinburgh (Innovation grants only)
- Tom Simpson – University of Bristol
- Liz Sockett – University of Nottingham
- Anthony Watts – University of Oxford
- David Williams – Discuva Ltd
- Nicola Williams – University of Liverpool
- Mark Woolhouse – University of Edinburgh
- Brendan Wren – London School of Hygiene and Tropical Medicine (Innovation grants only)
This theme will cover the discovery of new and revisit old small molecule approaches as well as developing novel treatments. Potentially building on discoveries in theme 1 as well as on existing validated targets, elements of this theme will be directed towards strategies designed to exploit chemical diversity for the identification of novel small molecule antibiotics. However, this theme also emphasises the importance of alternative approaches to treat resistant bacteria and develop new technologies for identifying resistant bacteria to underpin diagnostics development. This theme may provide a real-life test bed for bolt on projects/fellowships studying the impact of different economic and business models, or development of novel business models, related to the process and drivers of innovation in the development of new antibiotics and diagnostics.
One aim of this theme is to stimulate research to refresh the antibiotic pipeline. Old, shelved antibiotics and approved drugs with antibiotic potential could be revisited with new science and technology to enhance efficacy and reduce resistance potential. Antibiotics which have failed full human validation could be explored for their animal treatment potential. Genome mining for new synthetic pathways for antibiotics, bioengineering, synthetic biology, small molecule libraries with broader chemical space could be used. “Near miss” compounds could also be rescued using new, more targeted delivery methods. This will bring together basic bacteriologists with drug developers, chemists, synthetic biologists, materials scientists, mathematicians, biomedical engineers and physical scientists and engineers from both academia and industry.
Equally important, is the exploration of alternative treatment, for example, animal and human vaccines, ways of eliminating bacterial persistence, passive immunotherapy, bacteriophages, probiotics & antibacterial surfaces. The manipulation of the microbiome may also offer an alternative approach to prevent evolution and spread of resistant strains. Research into the scale up and manufacture of vaccines to resistant bacteria and novel antibiotic drugs and interaction with the private sector will be key to accelerate the translation of such new therapies.
Development of next generation diagnostics through the integration of cutting edge engineering and physical sciences with bacteriology could create simple, reliable, diagnostics for resistant bacteria in clinical and environmental settings. New diagnostics will also allow more targeted use of new antibacterial agents. Development of technological advances into new sensor systems will require partnership between industry and academia, and offers great opportunities for the private sector. Researchers should be mindful of the challenges associated with deploying new technologies in community settings, veterinary practices, care homes, farms etc. Such diagnostics may also form the basis of novel surveillance systems and this theme also includes development of new mathematical models to monitor the spread of resistant bacteria.
This is not an exhaustive list, this theme is open to innovative ideas but some aims are to:
- refresh the pipeline for antibiotics;
- develop new non-drug based treatments that can avoid resistance;
- develop rapid, point of care diagnostics to target these therapies;
- develop innovative diagnostics data linkages for community settings to monitor spread;
- develop physiologically relevant drug delivery systems; and
- consider the role of existing and new business models in encouraging innovation.
Prior to the launch of Theme 2 we invited interested parties to submit an expression of interest (EoI). From the EoIs received we selected individuals from a broad range of disciplines to attend one or more targeted workshops to encourage innovative thinking, networking of participants and development of proposals. The workshops took place in London (November–December 2014) and the report is available (PDF, 3.12MB).
- Duncan Maskell (Chair) – University of Cambridge
- Malcolm Walkinshaw (Deputy Chair) – University of Edinburgh
- Robert Beardmore – University of Exeter (innovation grants only)
- Gurdyal Besra – University of Birmingham (innovation grants only)
- Mervyn Bibb – John Innes Centre (innovation grants only)
- Marc Bonten – University Medical Center Utrecht, NL (innovation grants only)
- Martha Clokie – University of Leicester (innovation grants only)
- Jonathan Cooper – University of Glasgow
- Paul Edelstein - University of Cambridge and University of Pennsylvania (innovation grants only)
- Heather Fairhead – Phico Therapeutics
- Simon Foster – University of Sheffield (innovation grants only)
- Peter Fischer – University of Nottingham
- Martin Garnett – University of Nottingham
- Mary Helen Grant – University of Strathclyde (innovation grants only)
- David Haig – University of Nottingham
- Ian Henderson – University of Birmingham (innovation grants only)
- Kai Hilpert – St. Georges, University of London (innovation grants only)
- Alison Holmes – Imperial College London (innovation grants only)
- Rachel McKendry – University College London (innovation grants only)
- Calum McNeil – University of Newcastle
- Seamus O’Brien – AstraZeneca (innovation grants only)
- Lalita Ramakrishnan – University of Cambridge (innovation grants only)
- Daniel Ritz – Actelion Pharmaceuticals Ltd, Switzerland
- Jack Scannell – Innogen Institute, University of Edinburgh (innovation grants only)
- Mervyn Singer- University College London
- Sunil Shaunak – Imperial College London
- Neil Stokes – Redx Pharma
- Richard Titball – University of Exeter
- John Wain – University of East Anglia
- Jeffrey Watts – Zoetis, USA (innovation grants only)
- Sivaramesh Wigneshweraraj- Imperial College London (large collaboration grants only)
- Barrie Wilkinson – John Innes Centre (large collaboration grants only)
Theme 3: Understanding the real world interactions
It is clear that the environment and the way people and communities interact with the environment hugely influences the way bacteria behave and the transmission of genes within and between bacterial species.
A greater understanding of how differing environments and their uses influence the evolution, acquisition and spread of antibiotic resistance and reservoirs of resistance is therefore needed. Here the “environment” is seen in its broadest sense from host tissues to man-made settings and natural environments. This would encompass, for example, human and animal intestinal tracts, wounds in humans and animals, hospitals, care homes, transport systems and all the way through to waste water, agricultural and natural environments (freshwater, marine, soil, air, etc. and their interfaces). Understanding these environments and their role in resistance will help identify and target better prevention measures and management practices.
This theme, which will require close collaborations between medicine, life science, physical sciences, social sciences, engineering and the private sector, including the agricultural sector, will be fully scoped over the next few months and further details posted on this website when available.
Overall this theme will aim to deliver:
- Greater understanding of how resistant bacteria adapt to their environments and vice versa;
- Understanding the dynamics of community interaction and how this affects resistance and transmission;
- Ways to manipulate environments to prevent resistance evolution and transmission; and
- New surveillance networks across different environments
AMR in the built and indoor environment
The AHRC, working with RCUK partners, is leading on a funding call under Theme 3: Understanding Real World Interactions. The call, focusing on AMR in the built and indoor environment will be launched in November 2016. The call is expected to be for full proposals for pump-priming awards of up to £250,000 and up to 36 months duration. The deadline is expected to be in February 2017. We anticipate funding in the region of 8-12 projects.
AMR and the outdoor environment and host microbiome
To be confirmed
Theme 4: Behaviour within and beyond the health care setting
This theme will aim to elucidate the underpinning motivations for human behaviours relating to AMR, and how behaviour can affect development and spread of antibacterial resistance. It will also explore how to best enable effective behaviour change interventions in a variety of settings, relevant to both humans and animals. It may also serve as the basis for research into the economics of AMR.
Research in this area will draw on data from a range of sources – surveillance, health care, research and impact measures. It will, by definition, be interdisciplinary, linking clinical bacteriology, patient data and social science to investigate the uptake and use of new treatments, how they are being implemented and how to ensure appropriate stewardship to prevent resistance occurring.
This theme will, of necessity, take a broad understanding of the underpinning antecedents for behaviour, including the impact of different business models on antibiotic use in humans and animals. It will answer how economics and behaviour can come together to ensure a viable market for the development and sale of new treatments and diagnostics for resistant bacteria.
It could also be used to deliver some commissioned research, for example, health care providers may articulate a specific need in deliver or health services that our network of researchers may be well placed to addressed.
Ultimately, the aims will include:
- identify specific economic conditions, social norms and attitudes relating to antibiotics in order to develop context appropriate strategies;
- evaluate interventions to control/prevent the spread of resistant bacteria;
- assess the wider costs and benefits of behaviour change strategies;
- link surveillance data to stewardship practices to understand variance in impact; and
- develop and evaluate economic and regulatory models that balance the appropriate use of drugs and the mitigation of AMR while appropriately rewarding innovation
- David Armstrong (Chair) - King's College London
- Hilary Graham (Vice-Chair) - University of York
- Max Bachmann(Collaborative Grants Panels Only) - University of East Anglia
- Isabel Boyer - NIHR HTA lay member
- Ben Cooper - University of Oxford
- Leon Cruickshank - Lancaster University
- Radha D’Souza - University of Westminster
- John Fishwick (Collaborative Grants Panels Only) - Royal Veterinary College
- Annette Jeanes - University College London Hospitals
- Roger Jeffery - University of Edinburgh
- Ilias Kyriazakis - Newcastle University
- Maureen Mackintosh - Open University
- Mara Miele - Cardiff University
- Michael Millar - Bart's Health NHS Trust
- Jim Mills - University of Strathclyde
- Alison Pilnick (Collaborative Grants Panels Only) - University of Nottingham
- Claire Quinn - University of Leeds
- Mike Sharland (Collaborative Grants Panels Only) - St George’s, University of London
- Suzanne Skevington (Pump Priming Grants Panel Only) - University of Manchester
- Mervyn Singer - University College London
- Martin Smith - Agriculture and Horticulture Development Board (AHDB)
- Paul Wigley - University of Liverpool
This inter-disciplinary cross-council initiative will be focused on the four themes to supporting research encompassing academia, biopharma, diagnostic companies, veterinary and the health service.
Governance will be overseen by a top level Steering Group to provide scientific guidance and ensure delivery and an Executive Group of funding partners. Membership of the Steering Group will include experts that cross the remit of the research councils
Each theme will have its own Expert Scientific Panel to assess the research programmes.
- Herman Goossens (Chair) – University of Antwerp, Belgium
- Alastair Macdonald – The Glasgow School of Art
- Duncan Maskell – University of Cambridge, UK
- Rachel McKendry – University College London, UK
- David Payne - GlaxoSmithKline
- Sharon Peacock – University of Cambridge, UK
- Jared Silverman – VL32
- Richard Smith - London School of Hygiene and Tropical Medicine, UK
- Elizabeth Wellington – Warwick University, UK