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 需要资金购买 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产生的结晶实验，以识别结晶 我们的生物大分子的条件。 UTMB 有七个专门的蛋白质晶体学小组，如 以及一个用户设施，为使用蛋白质晶体学作为辅助技术的研究人员提供服务。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、免疫防御、癌症和糖尿病相关疾病，以及基本生物学 机制。靶标涵盖广泛的蛋白质、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具有挑战性：例如大型多域 大分子、三元蛋白质复合物、糖基化蛋白质和特定蛋白质：药物复合物，以便 在找到有希望的目标之前，我们经常需要筛选数千种结晶条件，这可以 用于生长适合高分辨率衍射实验的晶体。启用结构 确定，以及加速和降低目标结晶的成本，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 通过识别结晶与无定形蛋白质沉淀、蛋白质与盐晶体来推动科学进步； 2）图像 并以高分辨率和高速度评估数千个不同的结晶实验；和 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成约 1300 多个结晶板 （并且还在不断增加）由 NIH 的 1500 万美元资金 (9 R01s) 支持。我们无法获得有效的结晶 UTMB 的平板成像仪。从 Jan 购买 UVEX-PS600 系统和 CrystalDetect/WebView 软件 科学将使我们能够使用可见光和高分辨率有效地对结晶实验进行成像 和 UV 波长来识别有前途的晶体，并提供足够的成像能力来与 628 配合使用 一次结晶板无需人工干预。新仪器将安装在最近的 翻新 UTMB 的 Sealy 结构生物学和分子生物物理学中心 (SCSB)，并将获得支持 由SCSB。一名博士级 X 射线设施经理将在 SCSB 的全力支持下负责监督该系统。一个 由用户和独立专家组成的指导委员会将对 与准入、培训和维护相关的政策，并将由既定的咨询机构进行监督 委员会。 UVEX-PS600 系统将为我们的研究人员在 UTMB 开展 NIH 资助的项目提供服务 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 NIH 支持的竞争。此外，墨西哥湾沿岸联盟的成员将有权访问此 通过 SCSB 的设备对广泛的结构生物学项目进行试点实验。