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 要求提供资金，以购置一套JanSci UVEX-PS 600成像系统， 记录高通量筛选期间产生的结晶实验，以鉴定结晶 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， 以及一个用户设施，为研究人员使用蛋白质晶体学作为辅助技术。我们 研究人员利用结构生物学来研究涉及神经精神疾病的靶点， 传染病、免疫防御、癌症和糖尿病相关疾病，以及基本的生物学 机制等靶点跨越广泛的蛋白质，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具有挑战性：例如，大型多域 大分子、三元蛋白复合物、糖基化蛋白和特异性蛋白：药物复合物， 我们经常需要筛选数千种结晶条件，然后才能找到有希望的结果， 用于生长适用于高分辨率衍射实验的晶体。为了使结构 确定，以及加快和降低成本的结晶我们的目标，我们需要一个成像 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物，以及蛋白质与盐晶体，科学向前发展; 2）图像 并以高分辨率和高速度评估数千种不同的结晶实验;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多个结晶板 (and不断上升），得到NIH 1500万美元资金的支持（9个R 01）。我们无法获得一个有效的结晶体 UTMB的平板成像仪。从2011年1月起购买UVEX-PS 600系统和CrystalDetect/WebView软件 科学将使我们能够有效地成像结晶实验，并在高分辨率使用可见光和可见光 和紫外线波长，以确定有前途的晶体，并提供足够的成像能力，与628 在没有人工干预的情况下，一次结晶板。新仪器将于近期安装在 翻新的UTMB西利结构生物学和分子生物物理学中心（SCSB），并将得到支持 由SCSB。博士学位-由SCSB全力支持的一名X光设备经理将监督该系统。一 指导委员会由用户和正常距离专家组成，将监督 有关准入、培训和维护的政策，并将由一个既定的咨询机构监督。 以马克思UVEX-PS 600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;访问也将提供给用户在SCSB和新的教师，以促进他们的 竞争NIH的支持。此外，墨西哥湾沿岸财团的成员将有权获得这一 通过SCSB的设备进行广泛的结构生物学项目的试点实验。