High-throughput Crystallization Imaging System

与健康相关的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展，蛋白质结晶是阻碍整个结构测定过程的主要瓶颈，严重阻碍了研究进展。******此应用程序要求为最先进的，高容量结晶“酒店”和成像套件（“RockImager”）提供资金。该设备将允许研究人员在严格控制的环境中培养蛋白质晶体，使用可见光/紫外光光学系统自动筛选和成像数千种结晶条件，并从办公室或家用电脑上分析结果。该系统是西方迫切需要取代陈旧的蛋白质结晶设施，加快晶体发现过程，并创造一个高通量，开放访问的环境，这将给我们的研究小组一个国际竞争优势。******拟议的设备将支持nserc资助的来自伦敦地区西部和周边研究所的20多个研究小组的研究人员。它将加速参与钙信号、蛋白质降解、能量偶联和植物发育的蛋白质的结晶。随后的x射线结构将提供与帕金森病、癌症、抗生素发展和致病真菌毒素有关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患病状态下如何运作的基础。******该设备将通过提供一种现代的、系统的方法来缓解结晶瓶颈，并提高x射线结构的生产率，从而使多个研究项目受益。自动化成像系统将为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，用于设计限制疾病进展或对抗农业害虫和毒素的分子，这两者都是加拿大经济的沉重负担。该设备还将成为HQP培训和招聘的核心，岩石成像仪将使学生接触到最具竞争力的研究环境中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，该设备的收购，以及最近西方资助的对我们数据收集仪器的升级，对于获得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。* * * * *

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. *** **