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

CHNUK：从科学到政策的综合平台应对抗菌药物耐药性

• 批准号: MR/S014934/1
• 负责人: Christopher Dowson
• 金额: $ 254.74万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS014934%2F1
• 关键词: CHNUK; Integrated; platforms; science; policy

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.

抗击中国的抗菌素耐药性需要多管齐下，包括需要新的有效抗菌药。传统上，中国一直是仿制药的主要生产商，而不是开发商，但随着政府的新政策开始帮助推动药物发现的创新，时代正在发生变化。这包括对传统中药的结构性振兴，这些中药与其他已知的天然产品一起具有抗菌活性。很明显，有效的抗菌药，无论是作为单一疗法还是联合疗法，都是那些能够达到多个靶点的药物。传统中药本质上是组合式的，这为中国在中国抗击AMR的新有效疗法开发方面提供了一个黄金机会。在这里，我们汇聚跨学科团队，在英国和中国提供最先进的科学进步和政策专业知识；这将有助于培训下一代研究人员，开发创新的研究平台，并创造一个环境，使中国的抗生素研发能够成长和蓬勃发展，进入一个新的发现“黄金时代”。这是有可能实现的，我们将确定将影响和推动中国新抗生素的发现、开发和交付的关键途径和驱动因素。六个技术、政策和培训平台为未来的交付提供框架和基础，以及中国英国交流和互动的渠道。1.目标验证和机制。2.检测和筛选。3.引领发展4.产业翻译5.政策6.培训和交流。交流将是中心的重要组成部分，使多达15-20名研究人员能够交换到英国或中国。这包括文化培训、速成课程语言培训和谢菲尔德为中国研究员提供的广泛的高级研究培训项目，以及在Hub合作伙伴进行的长达12个月的专家研究培训。我们的重点将是“旧的”和“新的”目标，包括我们在基本过程、毒力和耐药性机制方面的广泛现有专业知识。我们的目标将是那些对ESKAPE和世卫组织优先考虑的细菌具有多重耐药性的细菌，包括大肠杆菌、幽门螺杆菌、铜绿假单胞菌、沙门氏菌。和金黄色葡萄球菌。这些病原体是大多数中国医院和社区危及生命的感染的罪魁祸首。迫切需要新的局部、胃部和全身治疗干预措施，以减少传播和疾病。CHN UK的这一活动中心建立在强大的大学和研究所合作基础上，合作伙伴包括中国科学院(CAS)、吉林上海药学院(SIMM)、英国皇家植物园(Kew)、谢菲尔德(Shefffield)、牛津大学(Oxford)、北京、华威、厦门。英国的钻石光源同步加速器、蛋白质生产英国(PPUK)和哈威尔(RCAH)的研究中心为这些项目奠定了基础；上海同步加速器(SINAP)和SIMM的国家化合物收集项目为中国项目奠定了基础。此外，这些活动将得到一个由学术界和工业界专家组成的国际小组的支持。这些专业知识包括在抗生素发现方面拥有超过250年经验的个人，在南非新成立的药物发现研究所(H3D)，以及来自普华永道(具有丰富的中国专业知识)和经济学人集团的全球抗菌药物研发行业和政策观点，这两家公司都致力于帮助鼓励全球抗菌药物研发解决方案的开发。经济学人集团已经计划了一个大型的国际AMR研讨会(伦敦，2019年1月)，我们将参与其中。一个由华威和谢菲尔德会说英语和中文的管理人员支持的高级管理小组将帮助有效地交付项目。

项目成果

AMR policy dialogue:driving innovative solutions for antimicrobial discovery

AMR 政策对话：推动抗菌药物发现的创新解决方案

• 发表时间: 2022
• 作者: Dowson CG

Plant peptidoglycan precursor biosynthesis: Conservation between moss chloroplasts and Gram negative bacteria

植物肽聚糖前体生物合成：苔藓叶绿体和革兰氏阴性细菌之间的保守性

• DOI: 10.1101/2022.01.05.475093
• 发表时间: 2022
• 作者: Dowson A

Plant peptidoglycan precursor biosynthesis: Conservation between moss chloroplasts and Gram-negative bacteria.

• DOI: 10.1093/plphys/kiac176
• 发表时间: 2022-08-29
• 期刊: PLANT PHYSIOLOGY
• 影响因子: 7.4
• 作者: Dowson, Amanda J.;Lloyd, Adrian J.;Cuming, Andrew C.;Roper, David, I;Frigerio, Lorenzo;Dowson, Christopher G.
• 通讯作者: Dowson, Christopher G.

Deliberate Next Steps toard a New Globalism for Universal Health Coverage

为实现全民健康覆盖而精心设计的后续步骤

• 发表时间: 2019
• 作者: Bloom G

To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority.

• DOI: 10.1021/acsinfecdis.0c00681
• 发表时间: 2021-08-13
• 期刊: ACS infectious diseases
• 影响因子: 5.3
• 作者: Cama J;Leszczynski R;Tang PK;Khalid A;Lok V;Dowson CG;Ebata A
• 通讯作者: Ebata A