High-throughput Crystallization Imaging System

高通量结晶成像系统

• 批准号: RTI-2019-00342
• 负责人: Shaw, Gary
• 金额: $ 10.87万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=664921
• 关键词: throughput; Crystallization; Imaging; System

Three dimensional structures of health-related proteins and their complexes are indispensable to identify proper protein function. The gold standard for three-dimensional protein structure determination is X-ray crystallography. With advances in data collection and structure determination, protein crystallization represents the major bottleneck that impedes the entire structure determination process and significantly inhibits research progress.******This application requests funding for a state-of-the-art, high-capacity crystallization “hotel” and imaging suite (“RockImager”). The proposed equipment will allow researchers to grow protein crystals in a tightly controlled environment, automatically screen and image thousands of crystallization conditions using visible/UV light optics and analyze results from their office or home computers. The system is urgently needed to replace antiquated protein crystallization facilities at Western, accelerate the crystal discovery process and create a high throughput, open-access environment that will give our research groups an internationally competitive edge.******The proposed equipment will support NSERC-funded researchers from more that 20 research groups at Western and surrounding institutes in the London region. It will expedite crystallization of proteins involved in calcium-signalling, protein degradation, energy coupling and plant development. The ensuing X-ray structures will provide atomic level details of proteins and complexes involved in Parkinson's disease, cancer, antibiotic development and disease-causing fungal toxins. Examination of these three-dimensional shapes are the foundation for understanding how these systems function in healthy and diseased states.******The proposed equipment will benefit multiple research programs by providing a modern, systematic approach that will alleviate the crystallization bottleneck and lead to increased X-ray structure productivity. The automated imaging system will provide PIs and HQP with huge time-savings allowing more efficient use of research time. Newly determined three-dimensional structures of proteins and complexes have the potential to be used as templates to design molecules that limit disease progression or combat agricultural pests and toxins, both heavy burdens on the Canadian economy. The equipment will also be central to training and recruitment of HQP where the RockImager will expose students to modern methods of crystallization required in the most competitive research environments. It will provide analytical and computational skills for HQP needed in academia, government agencies and biotechnology/chemical industries.******Overall the acquisition of this equipment, along with a recent Western-financed upgrade to our data collection instrument, is essential to gain fundamental insights into protein function with the potential for significant returns to the greater scientific community. *** **

健康相关蛋白质及其复合物的三维结构对于确定蛋白质的适当功能是必不可少的。三维蛋白质结构测定的金标准是X射线晶体学。随着数据收集和结构测定的进步，蛋白质结晶是阻碍整个结构测定过程并显着抑制研究进展的主要瓶颈。该申请要求为最先进的高容量结晶“酒店”和成像套件（“RockImager”）提供资金。拟议的设备将允许研究人员在严格控制的环境中生长蛋白质晶体，使用可见光/紫外光光学自动筛选和成像数千种结晶条件，并分析办公室或家用计算机的结果。迫切需要该系统来取代西部过时的蛋白质结晶设施，加速晶体发现过程，并创造一个高通量，开放获取的环境，使我们的研究小组具有国际竞争优势。拟议中的设备将支持来自伦敦地区西部和周边研究所的20多个研究小组的NSERC资助的研究人员。它将加速参与钙信号传导、蛋白质降解、能量耦合和植物发育的蛋白质的结晶。随后的X射线结构将提供帕金森病，癌症，抗生素开发和致病真菌毒素所涉及的蛋白质和复合物的原子水平细节。检查这些三维形状是了解这些系统在健康和疾病状态下如何运作的基础。拟议的设备将通过提供一种现代化的系统方法，减轻结晶瓶颈，提高X射线结构的生产率，使多个研究项目受益。自动成像系统将为PI和HQP节省大量时间，从而更有效地利用研究时间。新确定的蛋白质和复合物的三维结构有可能被用作模板，以设计限制疾病进展或对抗农业害虫和毒素的分子，这两种分子都给加拿大经济带来沉重负担。这些设备也将成为HQP培训和招聘的核心，RockImager将让学生接触到最具竞争力的研究环境所需的现代结晶方法。它将为学术界，政府机构和生物技术/化学工业所需的HQP提供分析和计算技能。总的来说，购买这台设备，沿着最近由西方资助对我们的数据收集仪器进行升级，对于获得对蛋白质功能的基本见解至关重要，并有可能为更大的科学界带来重大回报。 *** **