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

描述(申请人提供)：由X射线结晶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疗法的设计成为可能。这项提议寻求为加州大学圣地亚哥分校(UCSD)的NIH支持的研究人员购买一台X射线发生器和相关的光学设备。加州大学圣迭戈分校唯一一台也是唯一一台用于大分子结晶学的X射线发生器是1990年购买的一台过时的Rigaku FR-C。Rigaku FR-C需要大量维护，令人担忧的是，Rigaku不再支持Rigaku。这使得零件要么不可能买到，要么非常昂贵。随着FR-C上越来越多的部件出现故障，我们发现继续使用这台发电机变得越来越困难。为了解决这个问题，我们建议获得Rigaku MicroMaxTM 007HF及其相关光学元件(VariMaxTM)。(目前的光学系统不支持MicroMaxTM-007 HF的微焦光束。)家用X射线发生器在两个方面是必不可少的。首先，它提供了一种在同步加速器X射线源上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，家用光源使衍射性好的晶体可以在家里进行数据收集和结构确定，从而为具有挑战性的项目腾出宝贵的同步加速器时间。拟议的设备将取代大分子结晶设施目前的X射线发生器，后者有一名经验丰富的工作工程师管理日常操作，并将由现有的大分子结晶设施委员会管理。加州大学圣迭戈分校在X射线结晶学方面有着悠久的传统，这一承诺今天仍在继续。这一承诺从为化学和生物化学系以及斯卡格斯药学和药学学院的人员管理设备提供的财政支持中可见一斑。大分子结晶学设施还提出承诺提供资金，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用(即在充值的基础上)。加州大学圣迭戈分校有相当数量的X射线结晶学家，他们的研究工作依赖于定期获得家庭X射线源。简而言之，拟议的仪器对加州大学圣迭戈分校X射线结晶学的全校园成功至关重要。 与公共健康相关：由X射线结晶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疗法的设计成为可能。这项提议寻求获得一台X射线发生器和相关的光学装置，以便加州大学圣地亚哥分校的研究人员能够确定这种结构。这一设备将使这个校园里的一大批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。

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.