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：它雇用了超过 220,000 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。它以英国世界领先的健康和生命科学研究基地为基础。许多关键研究突破反过来又得益于工程和物理科学 (EPS) 研究的进步 - 这些研究提供了更加复杂的仪器和方法来支持生物体（从微生物到植物、动物和人体）的研究生物过程（包括疾病病理学和药物作用）。该生态系统各个部分的研发——从基础知识到应用研究再到产品开发——对于实现长期经济增长以及农业、粮食安全、医疗保健和公共卫生的持续进步至关重要。历史上的创新​​模式往往是线性的，涉及一定程度的偶然性。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：在哈韦尔科学与创新园区设有一个焦点（中心），与英国各地领先高等教育机构的正式发言人相连，它将整合学术界和工业界的互补专业知识，创建一个国家物理与生命科学融合方法开发卓越中心。RFI 的一个关键组成部分将是发展颠覆性能力，使生物活性小分子的发现更加高效和有效。生物活性小分子很重要，因为它们在处方药中占主导地位（>90%），并且可以用作更好地了解生物学的工具。目前的生物活性分子发现方法往往侧重于通过设计、合成、纯化和评估一组分子来一次研究一个设计理念。尽管经常使用自动化，但发现过程的各个阶段集成度很差。此外，使用有限的化学工具包来制备候选分子，这意味着过度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，更有效和高效地发现高质量的生物活性分子，其中所有阶段最终将在扩展的反应工具包的支持下完全集成。用于研究疾病生物学机制的化学工具的发现与该项目特别相关。该项目将受益于 Harwell 的其他关键科学能力，包括 Diamond Light Source 的 XChem 高通量晶体学设施。