CHNUK: Integrated platforms from science to policy in response to antibacterial resistance

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Combating Antimicrobial Resistance (AMR) in China requires a multi-pronged approach that includes the need for new effective antimicrobials.

Traditionally, China has been a major producer of generic antibiotics rather than a developer, but times are changing with new government policies that are beginning to help drive innovation in drug discovery. This includes the structured revitalization of Traditional Chinese Medicines (TCM), which, along with other natural products are known to possess antibacterial activities. It is very clear that effective antimicrobials, both those as monotherapy or in combination therapy, are those that hit multiple targets. Traditional Chinese Medicines (TCM) are by nature combinatorial in their activities and present a golden opportunity for China to take a strategic lead in the development of new effective therapeutics to combat AMR in China.

Here we bring together interdisciplinary teams to deliver state of the art scientific advances and policy expertise across the UK and China; that will help train the next generation of researchers, develop innovative research platforms, and an environment from which (given the support and incentives) antibiotic R&D in China could grow and flourish into a new 'golden age' of discovery. This is potentially achievable, and we will determine the critical pathways and drivers that will influence and enable the discovery, development and delivery of new antibiotics in China.

Six technology, policy, and training platforms provide the framework and foundation for future delivery, and a pipeline for China UK exchange and interaction. 1.Target validation and mechanisms. 2.Assays and screening. 3. Lead development 4. Industry translation 5. Policy. 6. Training and exchange. Exchange will be an important component of the hub enabling interchange of up to 15-20 researchers into the UK or China. This includes cultural orientation, crash course language training and a broad AMR training program at Sheffield for incoming China researchers, plus specialist research training for up to 12 months at hub partners. Our focus will be on 'old' and 'new' targets encompassing our breadth of existing expertise in essential processes, virulence and resistance mechanisms. Our targets will be those within multi-drug resistance in 'ESKAPE' and WHO priority bacteria including Escherichia coli, Helicobacter pylori, Pseudomonas aeruginosa, Salmonella sp. and Staphylococcus aureus. These pathogens are responsible for life-threatening infections in most Chinese hospitals and communities. New topical, gastric and systemic therapeutic interventions are urgently required to reduce transmission and disease.

This CHN UK hub of activity is built from strong university and institute partnerships across Chinese Academy of Sciences (CAS) Shanghai Institue Materia Medica (SIMM), Jilin, Royal Botanic Gardens at Kew, Sheffield, Oxford, Peking, Warwick, Xiamen. These are cornerstoned by national infrastructure support in the UK from the Diamond Light Source synchrotron, Protein Production UK (PPUK) and the Research Complex at Harwell (RCaH), and in China by the Shanghai Synchrotron (SINAP) and national compound collection at SIMM. Furthermore, these will be supported by an international panel of experts from academia and industry. This expertise includes individuals with more than 250 years combined experience in antibiotic discovery, the de novo establishment of a drug discovery institute (H3D) in South Africa, and global AMR industry and policy perspectives from PwC (with significant China expertise) and The Economist Group, both of whom are heavily committed to help encourage the development of global AMR solutions. The Economist Group have already planned a major international AMR workshop (London, Jan 2019) that we will engage with.

A senior management group supported by English and Chinese speaking administrators in Warwick and Sheffield will enable effective program delivery.

Technical Summary

We will
Bring together China and UK science and policy groups with industry, government advisors and funders, forming hubs to support platforms for fundamental and translational AMR discovery research targeting 'old' and 'new' essential processes, virulence and resistance mechanisms.
Develop new scientific methods and associated software platforms to combine high throughput natural product discovery with rapid chemical progression of fragment compounds from 'hit' to 'lead'.
Establish a China UK discovery pipeline from target to translation, with the combined natural product and fragment based lead discovery being a key element of our broad activities in AMR and allied fields.
Map capabilities and develop policy positions to influence funding and practice that will develop and strengthen the pipeline of AMR discovery R&D in China.
Enable substantive exchange programs to train and inform, across the wider breadth of disciples, the next generation of AMR researchers.
This will
Develop a robust research pipeline of AMR policy and discovery between China and the UK
Develop new capabilities and platforms at major national infrastructure investments (UK and Shanghai synchrotrons), automating high throughput structure determination at Shanghai with technology from the UK, driving the speed of hit chemical progression, and further pushing its bounds of productivity.
Develop a new generation of skilled and interconnected AMR researchers in China with a wide breadth of understanding and deep specialist training in 'state of the art' techniques
Develop new policy positions that will help influence and sustain AMR discovery funding, development and deployment in China.

Planned Impact

The focus of our proposed collaborative CHNUK: Integrated platforms from science to policy in response to antibacterial resistance meets ODA compliance across its main objectives in the promotion of future health and welfare in China, the lives of the most vulnerable people and in future economic development.

The project will use UK strengths in underpinning biology and science policy within UK academic groups and the platforms proposed within this application to maximise China's rich history and resources in natural products and traditional Chinese medicines. The China partners groups recognise these strengths and jointly we have developed an integrated programme of research, innovation and capacity building (from science to policy) to address the pressing need to combat antibiotic resistance in China, and in particular the lives of the most vulnerable people. Furthermore, China partners recognise that up-skilling within this programme will enable the proposed UK technology transfer to be used to its maximum effect. In the short term this, and fundamental research insights from UK research groups, will enable a step change in China researchers capabilities and policy for AMR discovery funding. In the mid to term all of this will enable more effective interaction with the emerging China drug discovery companies. There is already evidence of our China partners interacting with this industry sector in China, not only in the environment around Shanghai high-tech research parks, but also from activities in partners at Jilin and Xiamen. All of this will further accelerate this transfer and economic development underpinned by policy, enabled by the new skills and platforms developed from this programme. In the longer term the advances in knowledge developed by the partnership will help underpin the broader discovery of effective antibiotics in China that will be used to tackle the real and present threat to health in China that currently, disproportionately, afflicts the most vulnerable due to antibiotic resistant bacteria and lack of effect therapies.

Publications

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Bloom G (2019) Next steps towards universal health coverage call for global leadership. in BMJ (Clinical research ed.)

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Hu Q (2019) Detection of "Hidden" Antimicrobial Drug Resistance. in ACS infectious diseases

 
Description We have established an open source antibiotic discovery platform with academic and industry partners: providing a full breadth of expertise and reagents from previous discovery programs.

However, the major exchange program planned as part of this UK CHNA collaboration has had to be put on hold due to COVID-19. This has held back UK CHINA collaborations and a no cost extension will be sought to help meet currently unmet deliverables
Exploitation Route This early stage discovery program represents a a step change in how antibiotic discovery might progress.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://github.com/opensourceantibiotics
 
Description Research consortium has been an essential component in the establishment of open source antibiotic discovery https://github.com/opensourceantibiotics
First Year Of Impact 2020
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural

 
Description Civil Society Discussion on IACG Recommendations on Global Governance of AMR".
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Civil Society Discussions relating to Future Global Governance for Antimicrobial Resistance discussion paper publish July 2018
URL https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_Future_global_gover...
 
Description Wilton Park discussion of collaboration with China on global development
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Enabling public and private partnership platforms to accelerate antibiotic discovery
Amount £41,151 (GBP)
Funding ID 72691 EPSRC IAA Warwick 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 06/2022
 
Description Mapping capabilities and developing policy positions to influence funding and practice to develop and strengthen the pipeline of AMR discovery R&D in UK and China
Amount £64,000 (GBP)
Funding ID 72259 
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 01/2022 
End 03/2022
 
Description Strengthening China-UK Global Development Knowledge, Co-operation and Effectiveness A Research and Learning Platform for China International Development Research Network (CIDRN) Phase II
Amount £645,000 (GBP)
Organisation UK Department for International Development 
Sector Public
Country United Kingdom
Start 04/2019 
End 03/2022
 
Description Astra Zeneca inhibitor development 
Organisation AstraZeneca
Department Astra Zeneca
Country United States 
Sector Private 
PI Contribution Biochemical assay development and antimicrobial assays
Collaborator Contribution Development of an provision of target directed compound library and compounds with bioactivity
Impact Establishment of an open source discovery collaboration with industry engagement
Start Year 2020
 
Description Establishment of an open source antibiotic discovery consortium 
Organisation Diamond Light Source
Country United Kingdom 
Sector Private 
PI Contribution Biochemical assay development
Collaborator Contribution Gene cloning, optimisation, expression, protein production and crystallography
Impact Step change in international scientific collaboration : open source discovery with free exchange of ideas and results
Start Year 2020
 
Description Establishment of an open source antibiotic discovery consortium 
Organisation Northeastern University - Boston
Country United States 
Sector Academic/University 
PI Contribution Biochemical assay development
Collaborator Contribution Gene cloning, optimisation, expression, protein production and crystallography
Impact Step change in international scientific collaboration : open source discovery with free exchange of ideas and results
Start Year 2020
 
Description Establishment of an open source antibiotic discovery consortium 
Organisation Seattle Biomedical Research Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution Biochemical assay development
Collaborator Contribution Gene cloning, optimisation, expression, protein production and crystallography
Impact Step change in international scientific collaboration : open source discovery with free exchange of ideas and results
Start Year 2020
 
Description Establishment of an open source antibiotic discovery consortium 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Biochemical assay development
Collaborator Contribution Gene cloning, optimisation, expression, protein production and crystallography
Impact Step change in international scientific collaboration : open source discovery with free exchange of ideas and results
Start Year 2020
 
Description Life Arc inhibitor development 
Organisation LifeArc
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Development of biochemical assays, microbiology and structural biology
Collaborator Contribution Design development and provision of targeted chemical libraries including identification of bioactive molecules
Impact Establishment of industry interaction with an open source antibiotic discovery platform: scientific cultural change
Start Year 2020
 
Description New academic Collaboration : NEU USA 
Organisation Northeastern University - Boston
Country United States 
Sector Academic/University 
PI Contribution Development of new biochemical assays
Collaborator Contribution Computational chemistry design of novel antimicrobial inhibitors and provision of follow up medicinal chemistry
Impact Grant applications for follow up funding and establishment of an open source antibiotic discovery platform
Start Year 2020
 
Description New academic Collaboration : Shanghai Jiao Tong University 
Organisation Shanghai Jiao Tong University
Country China 
Sector Academic/University 
PI Contribution Access to results and reagents for a joint collaborative project
Collaborator Contribution New antimicrobial reagents requiring characterisation of mode and molecular mechanism of action
Impact Planned exchage of reagents and personnel. Funding has been acquired within China to enable this.
Start Year 2019
 
Description Research and Learning Platform for China International Development Research Network (CIDRN) 
Organisation China Agricultural University (CAU)
Country China 
Sector Academic/University 
PI Contribution We prepared a successful bid for funding by DFID and are focusing on building a network of partners in the UK and Europe to collaborate with a network of partners in China.
Collaborator Contribution The China Agricultural University is coordinating a network of partners in China with the aim of building China-UK joint research on areas of mutual interest.
Impact This is a multi-disciplinary partnership which includes several social sciences in addition to agricultural science, public health and public administration.
Start Year 2019
 
Description "Strengthen Multilateral Cooperation, Promote Better Global Health" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presentation by Lewis Husain to inform understanding and research / advisory work by key think tanks in China and central government.
Year(s) Of Engagement Activity 2020
 
Description Croucher Advanced Study Institute 2021 - Metals in Biology and Medicine: From Molecular Imaging to Drug Resistance 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact This course aims to disseminate the cutting-edge research about metals in biology and medicine to Hong Kong. The exploration of metals in biology and medicine is a fast-growing research area. Over the past decades, copper, iron and zinc have attracted enormous attentions due to the involvement of metals in aging and neuroscience. These metals can be detected and monitored in vivo by multi-techniques and multi-omics approaches, which further our understanding in metal homeostasis and metals in pathophysiological processes. This workshop aims to share some insightful views and ideas in molecular imaging and biosensing, metals in medicine, antibiotics and drug resistance
Year(s) Of Engagement Activity 2021
URL https://chemistry.hku.hk/events/seminars_conferences_detail/175/
 
Description IDS Blog on China and the future of global governance 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Blog published on the IDS website on China and the Future of Global Governance
Year(s) Of Engagement Activity 2020
URL https://www.ids.ac.uk/opinions/china-and-the-future-of-global-health-governance/
 
Description Influence BBC journalist to make radio programme on AMR in the marine environment 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Lewis Husain persuaded a BBC journalist to make a radio 4 programme on AMR in the marin environment, an ignored topic, and supported development of the concept
Year(s) Of Engagement Activity 2020
URL http://www.bbc.co.uk/programmes/m000mr6r
 
Description Natural Products, Students Against Superbugs Africa (SASA) webinar on AMR and drug development, 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Students Against Superbugs (SAS) Africa is a student-driven initiative under the guidance of qualified health professionals which seeks to mitigate the threat of Antimicrobial Resistance (AMR) in African communities using a One Health Approach with a keen focus on rural areas and urban informal settlements. We do this by empowering young people throughout Africa to be lead advocates in the fight against AMR. Young people account for majority of the population and are the future global leaders and stakeholders. Their active participation will play a huge role in curtailing this health burden. It is imperative that they are made aware of it early enough, and nurtured to help in transiting appropriate knowledge, attitudes, and practices to their respective communities.
Year(s) Of Engagement Activity 2021
URL https://www.studentsagainstsuperbugs.org/
 
Description Participation in WHO Western Pacific Regional Innovation Forum and Platform 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lewis Husain participated in workshop aimed at strengthening understanding of innovation and health in the Western Pacific region and development of an agenda for increased regional cooperation.
Year(s) Of Engagement Activity 2020
 
Description Policy briefing - Developing Health Diplomacy Capacity to Support Public Health in a Rapidly Changing World 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Policy briefing circulated to inform understanding and research / advisory work of key think tanks in China and to central government.
Year(s) Of Engagement Activity 2020
 
Description Radley College Lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Lecture topic - From Penicillins to Sensing Oxygen
Year(s) Of Engagement Activity 2021
 
Description Technical Support to an Evaluation of Ten Years of China's Health Reform 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Gerald Bloom and Wang Chenguang provided technical inputs to a major evaluation of ten years of China's health reform undertaken by the Government of China, the World Health Organization and the World Bank. A draft report is under review. The current plan is to publish the report for wide distribution in China and internationally. Gerald Bloom, co-authored a background paper on lessons emerging from international experience, including the increasing importance of digital health services and he helped produce a final draft report. Wang Chenguang led a team that assessed governance arrangements for implementing a major health system change process.
Year(s) Of Engagement Activity 2019
 
Description Towards world changing antibiotics, Janssen Research & Development, WHO World Antimicrobial Awareness Week, 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact World Antimicrobial Awareness Week (WAAW) is celebrated from 18-24 November every year. The 2021 theme, Spread Awareness, Stop Resistance, called on One Health stakeholders, policymakers, health care providers, and the general public to be Antimicrobial Resistance (AMR) Awareness champions.
Year(s) Of Engagement Activity 2021
URL https://www.who.int/campaigns/world-antimicrobial-awareness-week/2021
 
Description UK CHINA: CHNUK virtual workshops and research seminar series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presentation/ discussion with Brazilian microbiology groups as to how develop and work effectively as national and international consortia in AMR discovery
Year(s) Of Engagement Activity 2020
 
Description UK CHINA: CHNUK virtual workshops and research seminar series 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact To develop and deepen UK CHINA AMR discovery links both within the participants of Integrate CHNUK, other UK China and UK international research consortia, policy makers and the third sector. Looking for new ways of working and funding AMR research
Year(s) Of Engagement Activity 2020,2021
 
Description meeting with Department of Global Health at China National Health and Development Research Centre 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact On September 19, 2019 Gerald Bloom and Lewis Husain met with members of the Department of Global Health of the China National Health and Development Centre to discuss lessons learned about the design of activities for mutual learning between China and other countries on global health.The purpose of the meeting was to enable the participants in the discussion to draw on past experiences in designing a programme of work on this topic in collaboration with the Government. This will influence China's engagement in the health sector of a number of DAC-eligible countries in Africa and Asia.
Year(s) Of Engagement Activity 2019
 
Description participation in a research and innovation expert meeting convened by the Sino-European Health Networking Hub 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gerald Bloom and Lewis Husain were invited to participate in an expert consultation about joint European-Chinese health research and priorities for future funding. The consultation is part of a process for developing recommendations for the European Union.
Year(s) Of Engagement Activity 2020