Research Services Core (RSC)

研究服务核心 (RSC)

• 批准号: 10908198
• 负责人: Samuel Michael
• 金额: $ 473.89万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10908198
• 关键词: Acoustics; Aptitude; Astrocytes; Augmented Reality; Automation; Biological; Biological Assay; Biology; Biomanufacturing; Boston; Cancer Biology; Cells; Chemical Structure; Chemicals; Clinical; Collaborations; Collection; Communities; Complex; Computer software; Country; Custom; Dana-Farber Cancer Institute; Data; Data Analyses; Databases; Development; Device Designs; Devices; Dose; Drug Combinations; Emerging Technologies; Engineering; Ensure; Equipment; Evaluation; Feedback; Friends; Hospitals; Hybrids; Hypothalamic structure; Image; Incubators; Internet; Intramural Research Program; Laboratories; Libraries; Liquid substance; Maintenance; Measures; Methods; Mission; National Center for Advancing Translational Sciences; Nature; Neurobiology; Neurons; Neurosciences; Nociceptors; Patients; Peripheral; Phase; Process; Protocols documentation; Rare Diseases; Recording of previous events; Reporting; Research; Research Personnel; Research Support; Reservations; Retrieval; Robot; Robotics; Running; Sampling; Schedule; Scientist; Services; Site; Small Business Innovation Research Grant; Spottings; System; Technology; Testing; Time; Training; Tube; Universities; Validation; Vial device; Work; arm; assay development; cell bank; design; detector; flasks; follow-up; high throughput screening; imager; improved; induced pluripotent stem cell; instrument; instrumentation; medical schools; member; new technology; next generation; operation; preservation; response; scale up; screening; small molecule; stem cells; tissue culture; trophoblast; vigilance

1. Automation a. Two accepted phase 1 proposals for an Automated Flask Cleaning device design. 2 accepted phase 2 SBIR proposals for Augmented Reality for rare diseases. b. Instrumentation and Automation scheduling site stats Automation Scheduling had a total of 142 reservations, 185 protocols were run, 80+ total users registered. Instrumentation site had a total of 112 reservations for stand-alone devices (limited to overflow equipment from Outlook but expanding), there were also 133 maintenance requests to report issues on equipment (increasing) with 200+ registered users. c. 10 complex robotic platforms (ranging from the Primary screening robot to the fully automated BSL-3 system) and at least 250 pieces of regularly used equipment comprised of pintool transfer devices, solenoid valve small volume liquid dispensers, bulk dispensers and washers, acoustic transfer devices, robotic arms, incubators, centrifuges, plate sealers and peelers are maintained by RSC saving hundreds of thousands of dollars. d. Collaboration with DPI ETB members and Arimation Robotics to help design, build and implement an automation-friendly instrument to measure and collect data for Real Time Cellular Thermal Shift Assay (RT-CETSA). Design and testing phases complete with factory acceptance testing planned for September 2023. 2. Compound Management a. Automated tube reformatting and acoustic dispensing system designed, built custom for, and guided by NCATS compound management cutting edge needs. A straight from storage tube acoustic dispenser and a complex liquid handling platform was integrated with our compound store along with necessary peripherals for plate prep/preservation and decapping/capping capabilities to fully automated tube picking through assay ready plate creation while eliminating extra intermediate pipetting steps therefore reducing plastic consumables by 1/3 to 1/2 depending on the process. Installation, site acceptance testing, and training complete. Validation in process. b. Busiest year in history. 2,236 FOTS orders were filled for DPI biology groups and collaborators. Compounds requested 79% internally and 21% externally delivered around the country. c. 4,612 plates produced (acoustic 40% and non-acoustic 60%) for 771 orders. 65% were for Drug Combination, 27% for follow up plates, and 8% were qHTS style plates. 51% of the acoustic spotted plates were produced on our multiple automated acoustic platforms. 3. Automated Cell Technologies a. CellTrio System: RoboCell designed, custom built, and guided by NCATS cell technologies cutting edge needs to increase capability as well as scale up from existing Sartorius CompacT SelecT units. Includes flask handling, decappng/capping, detector, confluency inspection/imaging, complex liquid handling and dispensing as well as storage. Factory acceptance testing is ongoing to ensure necessary functionality. b. Five robotic high throughput biomanufacturing and functional differentiation processes of hiPSCs for Nocicenptors, Astrocytes, Trophoblasts, Hypothalamic neurons as well as adaptation of patient iPSCs in system and clean up. Supports internal (Stem Cell, 3DTBPL, etc) and numerous external collaborators. Involves direct involvement and feedback from scientists on process and evaluation. c. Nociceptors cell bank generated from 12 iPSC lines into 792 cryovials containing 5M cells/vial = 3.96B Nociceptor cells. Collaborators include Boston Childrens Hospital, Harvard Medical School, Department of Neurobiology, Dana Farber Cancer Institute, Department of Cancer Biology, and Nuffield Department of Clinical Neurosciences, The University of Oxford. Astrocytes cell bank generated from 14 iPSC lines into 392 cryovials containing 0.4M 10M cells/vial = 2.5B Astrocyte cells. Hypothalamic neurons generated from 3 iPSC lines into 91 cryovials containing 5M cells/vial = 455M Hypothalamic neurons.

1。自动化 一个。 两阶段的1阶段提案，用于自动化烧瓶清洁装置设计。 2公认的第2阶段SBIR提案提出了有关稀有疾病的增强现实的建议。 b。 仪器和自动化调度站点统计数据自动化计划总共有142份预订，185个协议，80个以上的用户注册。仪器网站总共有112个独立设备的预订（仅限于Outlook的溢出设备，但扩展），还有133条维护请求，以报告200多个注册用户的设备问题（增加）。 c。 10个复杂的机器人平台（从主要的筛选机器人到全自动的BSL-3系统）以及至少250件由Pintool传输设备，螺线管阀，小容量的液体分配器，散装分配器和垫圈，声学转移设备，机器人武器，机器人臂，培养箱，板层，密封器，pleerers和peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers和Peelers的Dolulers和Peelers neverers和Peelers seals和Peelers的销售设备，小型液体液体分配器，散装分配器和垫圈。 d。 与DPI ETB成员和Arimation Robotics合作，以帮助设计，构建和实施适合自动化的仪器，以测量和收集实时蜂窝热偏移分析（RT-CETSA）的数据。设计和测试阶段与计划于2023年9月计划的工厂接受测试一起进行。 2。复合管理 一个。 自动化管重新格式化和声音分配系统设计，构建定制和由NCATS复合管理尖端需求。从存储管声音分配器和复杂的液体处理平台中直接与我们的复合商店集成在一起，以及必要的外围设备，用于板制定/保存和替代/封盖功能，以通过测定准备板的创建进行全自动化管，同时消除了额外的中等移动性步骤，从而将塑料消耗置于1/3到1/2的过程中。安装，现场接受测试和培训完成。过程中的验证。 b。 历史上最繁忙的一年。 DPI生物学小组和合作者已填写2,236个FOTS订单。化合物在内部要求79％，外部21％在全国范围内分配。 c。 4,612个板（771个订单）生产（原声40％和非声学60％）。 65％用于毒品组合，27％用于随访板，QHTS型板8％。 51％的声斑板是在我们多个自动化的声学平台上产生的。 3。自动细胞技术 一个。 Celltrio系统：Robocell设计，自定义构建和由NCATS Cell Technologies Cutting需要提高功能以及从现有Sartorius紧凑型单元进行扩展。包括烧瓶处理，decappng/封盖，检测器，汇合检查/成像，复杂的液体处理和分配以及存储。正在进行工厂接受测试以确保必要的功能。 b。 五个机器人高吞吐量生物制造和功能分化过程，用于NOCICENPTORS，星形胶质细胞，滋养细胞，下丘脑神经元以及系统中患者IPSC的适应和清理。支持内部（干细胞，3DTBPL等）和许多外部合作者。涉及科学家对过程和评估的直接参与和反馈。 c。 伤害感受器的细胞库从12个IPSC线产生到792个cryovials，其中含有5M细胞/瓶= 3.96b伤害感受器细胞。合作者包括波士顿儿童医院，哈佛医学院，神经生物学系，达纳·法伯癌症研究所，癌症生物学系和牛津大学纳菲尔德临床神经科学系。星形胶质细胞的细胞库从14个IPSC线产生到392个cryovials，其中包含0.4M 10M细胞/小瓶= 2.5B星形胶质细胞。下丘脑神经元从3个IPSC线产生，分为91个含5M细胞/VIAL = 455M下丘脑神经元的冰冷。

项目成果

Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4.

• DOI: 10.1016/j.redox.2023.102719
• 发表时间: 2023-07
• 期刊: REDOX BIOLOGY
• 影响因子: 11.4
• 作者: Cheff, Dorian M.;Cheng, Qing;Guo, Hui;Travers, Jameson;Klumpp-Thomas, Carleen;Shen, Min;Arner, Elias S. J.;Hall, Matthew D.
• 通讯作者: Hall, Matthew D.

Application of temperature-responsive HIS-tag fluorophores to differential scanning fluorimetry screening of small molecule libraries.

• DOI: 10.3389/fphar.2022.1040039
• 发表时间: 2022
• 期刊: Frontiers in pharmacology
• 影响因子: 5.6

Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.

• DOI: 10.1371/journal.pone.0130796
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lee JA;Shinn P;Jaken S;Oliver S;Willard FS;Heidler S;Peery RB;Oler J;Chu S;Southall N;Dexheimer TS;Smallwood J;Huang R;Guha R;Jadhav A;Cox K;Austin CP;Simeonov A;Sittampalam GS;Husain S;Franklin N;Wild DJ;Yang JJ;Sutherland JJ;Thomas CJ
• 通讯作者: Thomas CJ

Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus.

• DOI: 10.1371/journal.pone.0166318
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cong Y;Dyall J;Hart BJ;DeWald LE;Johnson JC;Postnikova E;Zhou H;Gross R;Rojas O;Alexander I;Josleyn N;Zhang T;Michelotti J;Janosko K;Glass PJ;Flint M;McMullan LK;Spiropoulou CF;Mierzwa T;Guha R;Shinn P;Michael S;Klumpp-Thomas C;McKnight C;Thomas C;Eakin AE;O'Loughlin KG;Green CE;Catz P;Mirsalis JC;Honko AN;Olinger GG Jr;Bennett RS;Holbrook MR;Hensley LE;Jahrling PB
• 通讯作者: Jahrling PB

Serologic Cross-Reactivity of SARS-CoV-2 with Endemic and Seasonal Betacoronaviruses.

• DOI: 10.1007/s10875-021-00997-6
• 发表时间: 2021-07
• 期刊: Journal of clinical immunology
• 影响因子: 9.1
• 作者: Hicks J;Klumpp-Thomas C;Kalish H;Shunmugavel A;Mehalko J;Denson JP;Snead KR;Drew M;Corbett KS;Graham BS;Hall MD;Memoli MJ;Esposito D;Sadtler K
• 通讯作者: Sadtler K