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.

抽象的 要求资金购买JANSCI UVEX-PS600成像系统，以可视化，解释，评估和 记录在高通量筛选期间产生的结晶实验以识别结晶 我们生物大分子的条件。 UTMB有七个专用蛋白质晶体学组，作为 以及使用蛋白质晶体学作为辅助技术的研究人员为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研究涉及神经精神疾病的靶标， 传染病，免疫疾病，癌症和与糖尿病有关的疾病以及基本生物学 机制。靶标跨越广泛的蛋白质，蛋白质：蛋白质复合物，蛋白质：DNA复合物， 蛋白质：药物复合物和病毒。我们的许多目标都非常挑战：例如，大型多域 大分子，三元蛋白复合物，糖基化蛋白和特定蛋白：药物复合物，以便 我们通常需要在找到承诺命中之前筛选数千个结晶条件，这可以是 杠杆以生长适合高分辨率衍射实验的晶体。启用结构 确定，并加快和降低目标的成本，我们需要成像 可以有效识别成功结晶条件的系统。系统必须1）驱动 通过鉴定晶体与无定形蛋白沉淀和蛋白质与盐晶体，科学向前； 2）图像 并以高分辨率和高速评估数千个不同的结晶实验； 3） 在多用户环境中，从许多不同项目中处理大量的结晶数据。 目前，UTMB的结构生物学组每年产生〜1300+结晶板 （和上升）得到1500万美元的NIH资金（9 R01）的支持。我们无法访问工作结晶 UTMB的板成像仪。从JAN获取UVEX-PS600系统和CrystalDetect/WebView软件 科学将使我们能够使用两者可见地对结晶实验进行高效和高分辨率图像图像 紫外线波长具有有希望的晶体，并提供足够的成像能力与628合作 一次没有手动干预的结晶板。新乐器将安置在最近的 UTMB的改革后的SEALY SEALY结构生物学和分子生物物理学（SCSB），并将得到支持 由SCSB。由SCSB完全支持的博士学位X射线设施经理将监督系统。一个 由用户组成的指导委员会以及ARM的长度专家将提供监督 与访问，培训和维护有关的政策，并将由既定的咨询 委员会。 UVEX-PS600系统将为我们的调查人员提供在UTMB进行NIH资助的项目的服务， 涉及结构生物学；还将向SCSB和新教师提供访问权限 竞争NIH支持。此外，墨西哥湾海岸财团的成员将有权访问 通过SCSB进行设备，以在各种结构生物学项目上进行试验实验。