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Crystallization robotics to support X-ray crystallography at MUSC

结晶机器人为 MUSC 的 X 射线晶体学提供支持

基本信息

批准号：
8052518
负责人：
Christopher Davies
金额：
$ 12.49万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2012-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): With the advent of improved methods for phasing, the rate-limiting step to determine the structure of a macromolecular using X-ray crystallography is most often crystallization. The goal of crystallization is to find the best combination of parameters to produce crystals of sufficient quality so they can be used to generate high resolution diffraction data. Such a search involves testing an almost limitless number of parameters, including protein concentration, type of buffer and its pH, nature and concentration of precipitant, temperature, and use of additives or ligands. Hence, "crystallization space" is immense and if searched by low-throughput methods where crystal screens are pipetted manually, the process is severely limited by the amount of biological material that can be purified. The application of dispensing robots can dramatically change this situation because these can pipette protein in nanoliter volumes and therefore allow a much greater sampling of conditions with less biological material. Trays can also be set up considerably faster than manual methods. Although MUSC has a developing and thriving program in X-ray crystallography, including shared resources for protein production, our ability to produce crystal structures is severely hampered by the lack of crystallization robotics. This application aims to address that deficiency requesting the Phoenix RE nanoliter dispensing robot from Rigaku Inc. This will not only enhance the productivity of existing crystallography projects at MUSC, but will also stimulate new activity involving a wider group of investigators who aspire to use X-ray crystallography and have been unable to do so for lack of crystals. The broad benefits will be (a) the ability to tackle more challenging and potentially rewarding projects, including membrane proteins, (b) enhancement of the research environment at MUSC due to a greater emphasis on collaborative mechanistic studies of important biomedical problems that can be published in the higher impact journals, (c) increased competitiveness for NIH funding, (d) improved training environment for graduate students and post-docs and, (e) further development of X-ray crystallography and of structural biology in general through recruitment of new faculty. PUBLIC HEALTH RELEVANCE: This proposal requests funds to purchase crystallization robotics to enhance the X-ray crystallography facility that supports biomedical research at the Medical University of South Carolina. X-ray crystallography is a method of determining the structural details of macromolecules whose biological functions may be significant in human health and disease. Precise knowledge of the structure and function of such macromolecules contributes to better understanding of normal and abnormal biological processes and development of improved therapies to treat or cure major illnesses such as cancer, infectious diseases, inflammatory diseases and Alzheimer's disease.

描述（由申请人提供）：随着改进的定相方法的出现，使用X射线晶体学确定大分子结构的限速步骤通常是结晶。结晶的目标是找到最佳的参数组合，以产生足够质量的晶体，以便它们可以用于生成高分辨率衍射数据。这种搜索涉及测试几乎无限数量的参数，包括蛋白质浓度、缓冲液类型及其pH值、沉淀剂的性质和浓度、温度以及添加剂或配体的使用。因此，“结晶空间”是巨大的，并且如果通过手动移液晶体筛的低通量方法进行搜索，则该过程受到可以纯化的生物材料的量的严重限制。点胶机器人的应用可以极大地改变这种情况，因为这些机器人可以以纳升的体积吸取蛋白质，因此可以在生物材料较少的情况下进行更大的采样。托盘的设置速度也比手动方法快得多。虽然MUSC在X射线晶体学方面有一个不断发展和蓬勃发展的项目，包括蛋白质生产的共享资源，但由于缺乏结晶机器人技术，我们生产晶体结构的能力受到严重阻碍。本申请旨在解决这一缺陷，要求理学公司的Phoenix RE纳升点胶机器人。这不仅将提高MUSC现有晶体学项目的生产力，还将刺激新的活动，涉及更广泛的研究人员，他们渴望使用X射线晶体学，但由于缺乏晶体而无法这样做。广泛的好处将是：（a）能够解决更具挑战性和潜在回报的项目，包括膜蛋白，（B）由于更加强调可以在更高影响力的期刊上发表的重要生物医学问题的合作机制研究，因此增强了MUSC的研究环境，（c）增加了NIH资金的竞争力，（d）改善研究生和博士后的培训环境，（e）通过招聘新的教师，进一步发展X射线晶体学和结构生物学。公共卫生相关性：该提案要求提供资金购买结晶机器人技术，以增强南卡罗来纳州医科大学支持生物医学研究的X射线晶体学设施。X射线晶体学是一种确定大分子结构细节的方法，这些大分子的生物学功能可能对人类健康和疾病有重要意义。精确了解这些大分子的结构和功能有助于更好地理解正常和异常的生物过程，并有助于开发改进的治疗方法来治疗或治愈重大疾病，如癌症、传染病、炎症性疾病和阿尔茨海默病。