Acquisition of an automated crystal imager

购置自动晶体成像仪

• 批准号: 10410861
• 负责人: Gabrielle Rudenko
• 金额: $ 17万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2023-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410861
• 关键词: Advisory Committees; Biological; Biophysics; Communicable Diseases; Complex; Computer software; Crystallization; Crystallography; DNA; Data; Diabetes Mellitus; Disease; Doctor of Philosophy; Environment; Equipment; Faculty; Funding; Image; Immune; Intervention; Length; Maintenance; Malignant Neoplasms; Manuals; Molecular; Pharmaceutical Preparations; Policies; Proteins; Research Personnel; Resolution; Roentgen Rays; Science; Sea; Sodium Chloride; Speed; Structure; System; Techniques; Time; Training; United States National Institutes of Health; Virus; Work; arm; cost; crystallinity; experimental study; gulf coast; high throughput screening; imager; imaging system; instrument; macromolecule; member; neuropsychiatric disorder; protein complex; structural biology

ABSTRACT Funds are requested to acquire a JanSci UVEX-PS600 imaging system to visualize, interpret, evaluate and record crystallization experiments generated during high throughput screening to identify crystallization conditions for our biological macromolecules. UTMB has seven dedicated protein crystallography groups, as well as a User Facility that serves researchers using protein crystallography as a secondary technique. Our researchers leverage structural biology to investigate targets involved in neuropsychiatric disorders, infectious diseases, immune defense, cancer, and diabetes-related disorders, as well as basic biological mechanisms. The targets span a wide range of proteins, protein:protein complexes, protein:DNA complexes, protein:drug complexes, and viruses. Many of our targets are very challenging: for example, large multi-domain macromolecules, ternary protein complexes, glycosylated proteins and specific protein:drug complexes so that we often need to screen thousands of crystallization conditions before promising hits are found which can be leveraged to grow crystals suitable for high resolution diffraction experiments. To enable structure determination, as well as speed up and decrease the cost of crystallizing our targets, we need an imaging system that can efficiently identify successful crystallization conditions. The system must 1) drive the science forward by identifying crystalline vs amorphous protein precipitate, and protein vs salt crystals; 2) image and evaluate thousands of different crystallization experiments with high resolution and high speed; and 3) handle a very large amount of crystallization data from many different projects in a multi-user environment. Currently, the structural biology groups at UTMB are generating ~1300+ crystallization plates per year (and rising) supported by $15M in NIH funding (9 R01s). We have no access to a working crystallization plate imager at UTMB. Acquiring a UVEX-PS600 system and CrystalDetect/WebView software from Jan Scientific will enable us to image crystallization experiments efficiently and at high resolution using both visible and UV wavelengths to identity promising crystals, and provide enough imaging capacity to work with 628 crystallization plates at a time without manual intervention. The new instrument will be housed in the recently renovated Sealy Center for Structural Biology and Molecular Biophysics (SCSB) at UTMB, and will be supported by the SCSB. A Ph.D.-level X-ray Facility Manager, fully supported by the SCSB, will oversee the system. A steering committee composed of a mix of users, as well as arm’s length experts, will provide oversight of the policies relating to access, training, and maintenance, and it will be overseen by an established advisory committee. The UVEX-PS600 system will serve our investigators carrying out NIH-funded projects at UTMB that involve structural biology; access will also be provided to users at the SCSB and new faculty to facilitate their competition for NIH support. In addition, members of the Gulf Coast Consortium will have access to this equipment through the SCSB to perform pilot experiments on a wide range of structural biology projects.

摘要 需要资金以购买Jansci Uvex-PS600成像系统，以进行可视化、解释、评估和 记录高通量筛选过程中生成的结晶实验，以确定结晶 我们的生物大分子的条件。UTMB有七个专门的蛋白质结晶学小组， 以及为使用蛋白质结晶学作为二次技术的研究人员提供服务的用户设施。我们的 研究人员利用结构生物学来调查涉及神经精神障碍的目标， 传染病、免疫防御、癌症和糖尿病相关疾病以及基本生物学 机制。靶标跨越广泛的蛋白质，蛋白质：蛋白质复合体，蛋白质：DNA复合体， 蛋白质：药物复合体和病毒。我们的许多目标都非常具有挑战性：例如，大型多域 大分子、三元蛋白质复合体、糖基化蛋白质和特定蛋白质：药物复合体 我们通常需要筛选数千种结晶条件，然后才能找到有希望的匹配条件，这可能是 用来生长适合高分辨率衍射实验的晶体。启用结构 决心，以及加快和降低我们的目标结晶的成本，我们需要一个成像 该系统可以有效地识别成功的结晶条件。系统必须1)驱动 通过识别结晶型和非晶型蛋白质沉淀以及蛋白质和盐晶体来推进科学；2)图像 并对数千种不同的结晶实验进行高分辨率和高速度的评估；以及3) 在多用户环境中处理来自许多不同项目的大量结晶数据。 目前，UTMB的结构生物学小组每年生产约1300多块结晶板 (而且还在上升)得到了NIH 1500万美元资金的支持(9个R01)。我们无法接触到有效的结晶 UTMB的平板成像仪。从1月购买Uvex-PS600系统和CrystalDetect/WebView软件 科学将使我们能够高效和高分辨率地成像结晶实验，使用可见光 和UV波长来识别有希望的晶体，并提供足够的成像能力来处理628 结晶板一次完成，无需人工干预。这台新仪器将被安置在最近的 UTMB结构生物学和分子生物物理(SCSB)翻新的Sealy中心，并将得到支持 被南加州州立大学的。一名博士级别的X射线设备经理将监督该系统，并得到SCSB的全面支持。一个 由多名用户和保持距离的专家组成的指导委员会将监督 与访问、培训和维护相关的政策，并将由一个既定的咨询机构进行监督 委员会审议阶段。Uvex-PS600系统将为我们在UTMB执行NIH资助的项目的调查人员提供服务 涉及结构生物学；还将向SCSB的用户和新教员提供访问权限，以方便他们的 NIH支持的竞争。此外，墨西哥湾沿岸联盟的成员将可以访问 通过SCSB的设备，在广泛的结构生物学项目上进行中试实验。