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.

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