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UK - Department for Business, Energy and Industrial Strategy

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

Disclaimer: The data for this page has been produced from IATI data published by UK - Department for Business, Energy and Industrial Strategy. Please contact them (Show Email Address) if you have any questions about their data.

Project Data Last Updated: 27/08/2020

IATI Identifier: GB-GOV-13-FUND--Newton-MR_S014934_1

Description

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.

Objectives

Our objective is to drive a transformative response to antimicrobial resistance (AMR): by creating a vibrant and dynamic hub of research activities, and setting it within an integrated cohort of researchers at all levels, we will enable a step change in discovery, development, and implementation of AMR-targeted interventions. The hub will be durable and cohesive, integrating existing international endeavours and leveraging existing major research investments, in order to create a vehicle for the interchange of ideas and a critical mass of informed interdisciplinary researchers that will make breakthroughs in future healthcare in China, the UK and beyond We will: - Bring together world-class science and policy groups from UK and China, to form a hub of support platforms for fundamental and translational AMR discovery research. - Develop new scientific methods and associated software platforms to achieve high throughput natural product discovery from target to translation, tapping into the validated compound diversity inherent within traditional Chinese medicine to deliver a series of AMR targets highly enabled for translation. - Map capabilities and develop policy positions to influence funding and practice that will develop and strengthen the pipeline of AMR-targeted R&D and implementation in China and the UK. - Enable substantive exchange programs to train and inform, across the wider breadth of disciplines, the next generation of AMR researchers. Our objective and aims will be achieved through a series of integrated platforms, thereby "linking the pipeline": Platform 1: Target Validation and Mechanisms of essential processes, virulence and resistance mechanisms. This will deliver a robust pipeline of targets at all levels of development, drawn from ongoing fundamental research, making targets exploitable in the hub by solving their structures. Platform 2: Assays, fragment screening, natural products, and in silico design. This will deliver: hypersensitive biochemical assays for key targets to allow progressing compounds to potency; a novel approach to screening natural products, HTS affinity crystallography, using the XChem platform alongside fragment screening; design of fragment and natural product hit progression series, streamlined via optimized online tools. Platform 3: Hit to lead chemistry, bacteriology, toxicity and in vivo testing This platform will deliver lead compounds aimed towards commercial development. Platform 4: Policy This will deliver background data on R&D on antimicrobials in China; map key stakeholders, policies, regulations and other mechanisms; and interview stakeholders on factors influencing investment in R&D, and on possible incentive structures and collaboration mechanisms that can increase the quality and quantity of R&D. We will organise high-level workshops for scientists, policy-makers and regulators to discuss the findings and explore policy options. Platform 5: Translation and Industry This will deliver the translation of our nascent pipeline via a network of industrial partners. Platform 6: Knowledge Exchange This will deliver bespoke practical and theory training packages including research that will enhance the delivery of all platforms. It will instill a new multidisciplinary ethos in exchange students and researchers at all levels to drive a borderless response to AMR, enabling discovery to implementation within and beyond the hub.

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Budget

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