A High-throughput discovery facility for the Rosalind Franklin Institute

罗莎琳德·富兰克林研究所的高通量发现设施

• 批准号: EP/V011367/1
• 负责人: Benjamin Davis
• 金额: $ 257.64万
• 依托单位: Rosalind Franklin Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV011367%2F1
• 关键词: throughput; discovery; facility; Rosalind; Franklin

The Life Sciences sector forms a key part of the UK economy: it employs over 220,000 people, contributes significantly to GDP and UK balance of trade, and is crucial for developing leading-edge treatments for patients. It is underpinned by the UK's world-leading research base in the health and life sciences. Many key research breakthroughs are, in turn, enabled by advances in engineering and physical sciences (EPS) research - which provide ever more sophisticated instrumentation and methods to support the study of living organisms (from microbes to plants, animals and the human body) and biological processes (including both disease pathology and drug action). R&D across all parts of this ecosystem - from fundamental understanding to applied research to product development - is crucial for the delivery of long-term economic growth and continued advances in agriculture, food security, healthcare and public health. Historic models of innovation have often been linear, involving a degree of serendipity. Disruptive technologies and scientific breakthroughs will be accelerated if physical scientists, engineers, life scientists and industry work together, and at scale. This is the domain of the Rosalind Franklin Institute (RFI): with a focal point (Hub) at Harwell Science and Innovation Campus, linked to formal Spokes in leading HEIs across the UK, it will integrate complementary expertise from academia and industry to create a national centre of excellence for methods development at the convergence of the physical and life sciences.A key component of the RFI will be to develop disruptive capabilities to make the discovery of bioactive small molecules more efficient and effective. Bioactive small molecules are important since they dominate (>90%) prescribed drugs and they may be used as tools to provide a better understanding of biology. Current approaches to bioactive molecular discovery tend to focus on the investigation of one design idea at a time via the design, synthesis, purification and evaluation of sets of molecules. Although automation is often used, the stages of the discovery process are poorly integrated. Furthermore, a limited toolkit of chemistry is used to prepare candidate molecules, which means that undue focus is placed on specific classes of molecules: molecules which often do not have ideal properties for drug discovery programmes. The new facility will enable more effective and efficient discovery of high-quality bioactive molecules via rapid design-make-test-analyse cycles in which all stages will ultimately be fully integrated underpinned by an expanded reaction toolkit. The discovery of chemical tools that will be used to investigate disease biology mechanisms is of particular relevance to this project. The project will benefit from other key scientific capabilities at Harwell, including the XChem high-throughput crystallography facility at Diamond Light Source.

生命科学行业是英国经济的重要组成部分：它拥有超过22万名员工，对GDP和英国贸易平衡做出了重大贡献，对于为患者开发领先的治疗方法至关重要。它以英国在健康和生命科学方面世界领先的研究基地为基础。反过来，工程和物理科学（EPS）研究的进步使许多关键的研究突破成为可能，这些研究提供了越来越复杂的仪器和方法，以支持对活生物体（从微生物到植物、动物和人体）和生物过程（包括疾病病理学和药物作用）的研究。整个生态系统的研发——从基础认识到应用研究再到产品开发——对于实现长期经济增长和农业、食品安全、医疗保健和公共卫生领域的持续进步至关重要。历史上的创新模式往往是线性的，涉及一定程度的意外发现。如果物理科学家、工程师、生命科学家和工业界大规模合作，颠覆性技术和科学突破将会加速。这是罗莎琳德·富兰克林研究所（RFI）的领域：在哈维尔科学与创新校区设有一个中心（Hub），与英国领先的高等教育机构的正式辐条联系在一起，它将整合学术界和工业界的互补专业知识，创建一个国家卓越中心，用于物理和生命科学的融合方法开发。RFI的一个关键组成部分将是开发颠覆性能力，使生物活性小分子的发现更加高效和有效。具有生物活性的小分子很重要，因为它们在处方药中占主导地位（大约90%），而且它们可以作为更好地理解生物学的工具。目前的生物活性分子发现方法倾向于通过设计、合成、纯化和评估一组分子，一次只研究一种设计思想。虽然经常使用自动化，但发现过程的各个阶段集成得很差。此外，用于制备候选分子的化学工具有限，这意味着过分关注特定类别的分子：这些分子通常不具有药物发现计划的理想特性。新设施将通过快速的设计-制造-测试-分析循环，使高质量生物活性分子的发现更加有效和高效，其中所有阶段最终将在扩展的反应工具包的基础上完全集成。发现用于研究疾病生物学机制的化学工具与本项目特别相关。该项目将受益于哈维尔的其他关键科学能力，包括钻石光源的XChem高通量晶体学设备。