University of Warwick - Equipment Account

华威大学 - 设备帐户

• 批准号: EP/K011618/1
• 负责人: Caroline Meyer
• 金额: $ 978.26万
• 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: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK011618%2F1
• 关键词: University; Warwick; Equipment; Account

This proposal is to design, build, validate and exploit the features of a new Raman spectrometer that will collect Raman, Raman Optical Acitity (ROA), and Raman Linear Difference (RLD) spectra. ROA is well-established, but comparatively under-used as a means of probing secondary and tertiary structures of proteins and other biomacromolecules. RLD is a newly invented technique (Rodger et al. Analytical Chemistry, 2012) that can be used to give relative orientations of subunits of complex molecular assemblies. Raman spectroscopy provides access to the wealth of information available in vibrational spectroscopy without the challenges which confront infra red absorbance where water signals dominate. This project builds on the investigators' acknowledged expertise in developing novel spectroscopies for the study of biomolecules. It follows their success (measured by the increase in publications and linear dichroism (LD) instrument sales triggered by their work over the past 10 years) in making UV-LD an available technology. The motivation for developing a new form of spectroscopy is that the structures and arrangements of molecules, including sugars and lipids, that play key roles in the structures and functions of biomacromolecules are invisible to many techniques. Further, existing techniques do not provide sufficient information for many applications. Atomic-level techniques including crystallography and NMR are not well-suited to large irregular molecular assemblies where the structures of both the macromolecule and surrounding molecules contribute to the function of the components. Circular dichroism, which is currently the most widely used method for determining solution-phase secondary structures of proteins, has comparatively low information content and usable concentration ranges. Thus we need alternative approaches to provide the required information. We believe different forms of Raman spectroscopy can contribute to addressing these issues, but the required instrumentation has not yet been invented. The main applications of the instrument in the lifetime of the funding will be:1. Understand atomic-level structures and functions of biomacromolecules in cellular assemblies which is essential if we wish to control biological processes, such as cell division, for disease control and biotechnology applications. 2. Enhance efficiency in the development and production of pharmaceutical (small molecule) and biopharmaceutical (proteins, nucleic acids, viruses, bacteria) products by improving the approach to Process Analytical Technology (PAT) and helping to enable 'Quality by Design' (QbD). The hypothesis underlying QbD for pharmaceutical drugs, is that quality in production can be planned, and that most quality crises and problems relate to the way in which quality was (or was not) planned in the first place. QbD operates fairly effectively in the pharmaceutical industry. Regulators such as the European Medicines Agency are looking to expand the concept and process of QbD from pharmaceutical products to biopharmaceuticals. However, the analytical methodologies that are possibly sufficient for pharmaceuticals are clearly not adequate for biopharmaceuticals. New challenges are also being brought by the emerging 'Biosimilars' market: most simply, what is 'highly similar'? A wide user community will be established. The applications of the first users will be mainly with proteins, protein fibres, protein assemblies including bacteriophage, and membrane systems.

本提案旨在设计、构建、验证和利用一种新的拉曼光谱仪的功能，该光谱仪将收集拉曼、拉曼光学活性（罗阿）和拉曼线性差（RLD）光谱。罗阿是完善的，但相对不足的使用作为一种手段，探测蛋白质和其他生物大分子的二级和三级结构。RLD是一种新发明的技术（Rodger等人，Analytical Chemistry，2012），其可用于给出复杂分子组装体的亚基的相对取向。拉曼光谱学提供了对振动光谱学中可用的丰富信息的访问，而没有面临水信号占主导地位的红外吸收的挑战。该项目建立在研究人员在开发用于生物分子研究的新型光谱学方面公认的专业知识的基础上。它遵循他们的成功（通过过去10年来他们的工作引发的出版物和线性二色性（LD）仪器销售的增加来衡量），使UV-LD成为一种可用的技术。开发一种新形式的光谱学的动机是，在生物大分子的结构和功能中起关键作用的分子（包括糖和脂质）的结构和排列对许多技术是不可见的。此外，现有技术不能为许多应用提供足够的信息。包括晶体学和NMR的原子级技术不太适合于大的不规则分子组装体，其中大分子和周围分子的结构都有助于组件的功能。圆二色谱法是目前测定蛋白质溶液相二级结构最广泛使用的方法，其信息量和可用浓度范围相对较低。因此，我们需要其他方法来提供所需的信息。我们相信不同形式的拉曼光谱可以有助于解决这些问题，但所需的仪器尚未发明。该工具在资金有效期内的主要应用将是：1。了解细胞组装中生物大分子的原子级结构和功能，如果我们希望控制疾病控制和生物技术应用的生物过程，如细胞分裂，这是必不可少的。2.通过改进过程分析技术（PAT）方法和帮助实现“质量源于设计”（QbD），提高制药（小分子）和生物制药（蛋白质、核酸、病毒、细菌）产品的开发和生产效率。制药QbD的基本假设是，生产质量是可以计划的，大多数质量危机和问题都与质量最初计划（或不计划）的方式有关。QbD在制药行业的运作相当有效。欧洲药品管理局等监管机构正在寻求将QbD的概念和过程从药品扩展到生物制药。然而，可能足以用于制药的分析方法显然不足以用于生物制药。新兴的“生物仿制药”市场也带来了新的挑战：最简单的是，什么是“高度相似”？将建立一个广泛的用户社区。第一批用户的应用将主要是蛋白质、蛋白质纤维、蛋白质组装体（包括噬菌体）和膜系统。

项目成果

Towards increased reliability by objectification of Hazard Analysis and Risk Assessment (HARA) of automated automotive systems

• DOI: 10.1016/j.ssci.2017.03.024
• 发表时间: 2017-11-01
• 期刊: SAFETY SCIENCE
• 影响因子: 6.1
• 作者: Khastgir, Siddartha;Birrell, Stewart;Jennings, Paul
• 通讯作者: Jennings, Paul

Calibrating trust through knowledge: Introducing the concept of informed safety for automation in vehicles

• DOI: 10.1016/j.trc.2018.07.001
• 发表时间: 2018-11-01
• 期刊: TRANSPORTATION RESEARCH PART C-EMERGING TECHNOLOGIES
• 影响因子: 8.3
• 作者: Khastgir, Siddartha;Birrell, Stewart;Jennings, Paul
• 通讯作者: Jennings, Paul

Systems Approach to Creating Test Scenarios for Automated Driving Systems

• DOI: 10.1016/j.ress.2021.107610
• 发表时间: 2021-03
• 期刊: Reliab. Eng. Syst. Saf.
• 作者: S. Khastgir;S. Brewerton;John Thomas;P. Jennings