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X-ray generator and associated optics for macromolecular crystallography at UCSD

加州大学圣地亚哥分校用于大分子晶体学的 X 射线发生器和相关光学器件

基本信息

批准号：
8246289
负责人：
PARTHO GHOSH
金额：
$ 39.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2013-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The structures of biological macromolecules determined by X-ray crystallography provide an unparalleled level of detailed information and make possible the design of therapeutics aimed at treating human illnesses. This proposal seeks to acquire an X-ray generator and associated optics for NIH-supported investigators at the University of California, San Diego (UCSD). The one and only X-ray generator for macromolecular crystallography at UCSD is an antiquated Rigaku FR-C that was purchased in 1990. The Rigaku FR-C requires a great deal of maintenance, and worryingly is no longer supported by Rigaku. This makes parts either impossible to get or very expensive. As more and more parts break down on the FR-C, we are finding it increasingly difficult to continue operation with this generator. To solve this problem, we propose to acquire a Rigaku MicroMaxTM 007 HF and its associated optics (VariMaxTM). (The current optics will not support the microfocus beam of the MicroMaxTM-007 HF.) A home X-ray generator is essential in two ways. First, it provides a means for screening crystals (including cryopreservative conditions) for diffraction prior to data collection at a synchrotron X-ray source. Without such screening, data collection at the synchrotron would need to be carried out in blind and wasteful fashion. Second, a home source enables data collection and structure determination to be carried out at home for crystals that diffract well, freeing up valuable synchrotron time for challenging projects. The proposed equipment will replace the current X-ray generator in the Macromolecular Crystallography Facility, which has an experienced staff engineer who manages daily operations, and will be administered by the existing Macromolecular Crystallography Facility Committee. UCSD has a long tradition of X-ray crystallography, and this commitment continues today. This commitment is evidenced by financial support for personnel to manage the equipment from the Department of Chemistry & Biochemistry and the Skaggs School of Pharmacy and Pharmaceutical Sciences. The Macromolecular Crystallography Facility has also offered to commit funds to pay for the costs of removal and disposal of the current X-ray generator. The long-term support of the equipment will be derived from user fees (i.e., on a recharge basis). UCSD has a substantial number of X-ray crystallographers whose research efforts depend on regular access to a home source of X-rays. In short, the proposed instrumentation is crucial to the campus-wide success of X-ray crystallography at UCSD. PUBLIC HEALTH RELEVANCE: The structures of biological macromolecules determined by X-ray crystallography provide an unparalleled detailed level of information and make possible the design of therapeutics aimed at treating human illnesses. This proposal seeks to obtain an X-ray generator and associated optics to enable such structure determination by investigators at the University of California, San Diego. This equipment will enable a large group of biomedical scientists at this campus to gain fundamental knowledge relevant to human diseases, and to apply this knowledge to therapeutics.

描述（由申请人提供）：通过X射线晶体学确定的生物大分子结构提供了无与伦比的详细信息，并使旨在治疗人类疾病的治疗方法的设计成为可能。该提案旨在为加州大学圣地亚哥分校（UCSD）的NIH支持的研究人员购买X射线发生器和相关光学器件。UCSD唯一的大分子晶体学X射线发生器是1990年购买的一台过时的理学FR-C。理学FR-C需要大量的维护，令人担忧的是理学不再支持。这使得零件要么不可能得到，要么非常昂贵。随着越来越多的部件在FR-C上发生故障，我们发现越来越难以继续使用该发电机。为了解决这个问题，我们建议购买理学MicroMaxTM 007 HF及其相关光学器件（VariMaxTM）。(The当前的光学器件将不支持MicroMaxTM-007 HF的微聚焦光束。家用X射线发生器在两个方面至关重要。首先，它提供了一种在同步加速器X射线源收集数据之前筛选晶体（包括低温保存条件）进行衍射的方法。如果没有这样的筛选，同步加速器的数据收集将需要以盲目和浪费的方式进行。其次，家庭来源使数据收集和结构确定能够在家里进行，晶体的折射率很好，释放宝贵的同步加速器时间具有挑战性的项目。拟议的设备将取代高分子晶体学设施现有的X射线发生器，该设施有一名经验丰富的工程师管理日常业务，并将由现有的高分子晶体学设施委员会管理。UCSD在X射线晶体学方面有着悠久的传统，这一承诺一直延续到今天。这一承诺证明了人员的财务支持，以管理从化学和生物化学系和药学和制药科学的斯卡格斯学院的设备。高分子晶体学融资机制还表示愿意承付资金，以支付拆除和处置现有X射线发生器的费用。设备的长期支持将来自用户费（即，在再充电的基础上）。UCSD拥有大量的X射线晶体学家，他们的研究工作依赖于定期获得家庭X射线源。简而言之，所提出的仪器是至关重要的校园范围内的成功的X射线晶体学在加州大学圣地亚哥分校。公共卫生相关性：通过X射线晶体学确定的生物大分子结构提供了无与伦比的详细信息，并使旨在治疗人类疾病的治疗方法的设计成为可能。该提案旨在获得X射线发生器和相关的光学器件，以使加州大学圣地亚哥分校的研究人员能够确定这种结构。该设备将使该校区的一大群生物医学科学家能够获得与人类疾病相关的基础知识，并将这些知识应用于治疗学。