NCI Program for Natural Products Discovery - Cures

NCI 天然产物发现计划 - 治愈

• 批准号: 10487021
• 负责人: Barry Okeefe
• 金额: $ 13.96万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/10487021
• 关键词: Academic Medical Centers; Africa; African; Agreement; Analytical Chemistry; Antineoplastic Agents; Australia; Automation; Basic Science; Bioinformatics; Biological; Biological Assay; Biological Process; Biology; CCR; Chemical Structure; Chemicals; Code; Collaborations; Collection; Communities; Contracts; Country; Databases; Department of Defense; Division of Cancer Treatment and Diagnosis; Europe; Extramural Activities; Freeze Drying; Funding; Genomics; Health; Human; India; Individual; Infrastructure; Institutes; Institution; International; Investments; Iowa; Joints; Libraries; Liquid substance; Location; Malignant Neoplasms; Manuscripts; Maps; Medicine; Methods; Michigan; Microbe; Mississippi; Modernization; National Institute of Allergy and Infectious Disease; Natural Products; Natural Products Chemistry; Oklahoma; Organism; Participant; Process; Production; Protocols documentation; Publishing; Recording of previous events; Records; Reporting; Research; Research Activity; Research Institute; Research Personnel; Resources; Robotics; Sampling; Science; Shipping; Ships; Soil; Sorting - Cell Movement; Source; Specimen; Structure; Sweden; System; Taxonomy; Technology; Technology Transfer; Testing; Texas; United Kingdom; United States; United States National Institutes of Health; Universities; Vial device; anticancer research; base; citizen science; college; database structure; drug development; drug discovery; fungus; high throughput screening; material transfer agreement; medical schools; microorganism; microorganism culture; molecular oncology; new technology; preservation; programs; repository; robotic system; screening; screening program; translational pipeline; voucher

Accomplishments: Aim 1. Create new technologies to build an enhanced NP pre-fractionated library amenable to modern high-throughput targeted screening programs. -New high-throughput natural products chemistry infrastructure has been built, outfitted and implemented on the NCI at Frederick campus on Ft. Detrick. Implemented technologies enable the production of up to 175,000 fractionated natural product samples per year as well as the automated storing and sorting of up to 1,100,000 fractions and the plating (in 384-well plates) of 5,000,000 test samples per year. -The NPNPD has helped create new robotic systems, enhanced lyophilization capabilities, automated purification and analytical chemistry systems, liquid handling systems and integrated robotic interfaces between these automated systems. -The NPNPD has written code for new automation programs for the creation, annotation, storage, plating drying, and purification of natural product samples. -These technologies and programs have already been successfully transferred to additional research institutes (Univ. Michigan, Univ. Mississippi, and the University of Pretoria, S. Africa). Aim 2. Expand the chemical diversity available to the public from culturable microorganisms with new methods and libraries. -The NPNPD has built, outfitted and implemented new facilities and methods for the high-throughput cultivation and extraction of microorganisms at the NCI at Frederick campus on Ft. Detrick. -The NPNPD has created, through a contract with the University of Oklahoma Citizen Science Program a library of 13,000 individual soil fungi collected throughout the United States. The NPNPD has processed, photographed, cultured and determined the ITS sequence and taxonomy of all of these samples. -The NPNPD has so far cryo-vialed 100,000 individual culture vials of fungi accessioned by the NCI for preservation and distribution of this resource. -The NPNPD has completed acquisition of 6700 Australian marine microbes from the Australian Institute of Marine Science. -Initial liquid cultivation, extraction and prefractionation protocols for fungi have been reduced to practice. Aim 3. Provide the pre-fractionated library to screening centers worldwide to accelerate drug discovery. -The NPNPD has so far produced 450,000 pre-fractionated extracts and plated 18,000,000 wells on 28,000 384-well plates for distribution. -The NPNPD has made available to the public 326,000 individual pre-fractionated natural product samples in 384-well plates. -The NPNPD shipped 4,500,000 screening samples so far (more than the combined shipments of NCI natural product samples throughout the previous 40 year history of the NCI Natural Products Repository). -The NPNPD has so far received and processed 60 requests for material transfer agreements (MTAs) from research organization around the world to enable these centers to screen NPNPD pre-fractionated natural product samples. -The NPNPD has so far completed 30 individual MTAs with research institutions worldwide (see Appendix section for a detailed list). -The NPNPD published a manuscript on this specific aim in ACS Chemical Biology in 2018, it was the cover article. Aim 4. Provide high throughput screening support for researchers to enable targeted discovery efforts. -The NPNPD has entered into joint research agreements with NIAID, NCATS, NCCIH, the Department of Defense, and Astra Zeneca UK to pursue joint drug discovery efforts using NPNPD pre-fractionated libraries. -The NPNPD has successfully supported multiple screens for researchers at the CCR, Univ. of Texas, Univ. of Iowa, Vanderbilt Univ., Baylor College of Medicine, Yale Medical School, Walter Reed Army Institute of Research, NIAID, and Astra Zeneca. -The NPNPD is a participant in a funded international research program let by University of Pretoria (S. Africa) which will use NPNPD technologies to develop a library of fractions of African origin to be screened in Africa, Australia, India, Europe, the United Kingdom and the NCI. -The NPNPD published a manuscript on this specific aim in Natural Product Reports in 2020, it was the cover article. Aim 5. Provide faster analytical resources (isolation, structure elucidation, re-supply) to expedite translational pipelines. -The NPNPD has created, outfitted and implemented high-throughput secondary purification and analytical chemistry capabilities at the NCI at Frederick campus on Ft. Detrick. -The NPNPD has created the capability to perform up to 500 purifications together with plating and drying of 10,000 sub-fraction samples per week. -The NPNPD has successfully utilized this capability on several programs with the CCR/NCI, Astra Zeneca and the Department of Defense. -The NPNPD produced and shipped 25,000 purified subfractions derived from active NPNPD fractions to screening centers. -The NCI has transferred these technologies to the University of Mississippi and University of Pretoria, S. Africa, and Sweden. -The NPNPD published a manuscript on this specific aim in ACS Chemical Biology in 2020, it was the cover article. Aim 6. Establish a public database and bioinformatics platform to broaden input and expand impact. -The NPNPD is in the process of modernizing legacy natural product databases to bring them into more modern and easily compatible database structures. These databases include information on taxonomy, amount, collection location information, photographs of source organisms, voucher collections at the Smithsonian Institution, shipping records, bioassay results, analytical chemistry files (including chemical structures, NMR, IR and MS files) etc. -The NPNPD has reached agreement with the Smithsonian Institution and NIH to include the NCI Natural Product Voucher Collection as an Institutionally Significant Scientific Collection to be protected in perpetuity. This agreement includes aspects of public access to voucher specimens. -The NPNPD has developed Self-Organizing Map (SOM) bioinformatic systems for the rapid prioritization of natural products chemistry efforts based on analysis of their biological activity. -The NPNPD published a manuscript on this specific aim in Molecular Oncology in 2021, it was the cover article.

成就：目标1。创建新技术，以建立一个可容纳现代高通量目标筛查程序的增强的NP预分级图书馆。 - 新高通量天然产品化学基础设施已在FT的Frederick校园内建立，装备和实施。迪特里克。实施的技术可每年生产多达175,000个分数的天然产品样品，以及每年最多1,100,000个分数的自动储存和分类（384孔板），每年5,000,000个测试样品。 - NPNPD帮助创建了新的机器人系统，增强的冻干功能，自动化纯化和分析化学系统，液体处理系统以及这些自动化系统之间的集成机器人接口。 - NPNPD为新的自动化程序编写了代码，用于创建，注释，存储，镀干和自然产品样品的纯化。 - 这些技术和计划已经成功地转移到其他研究机构（密西根大学，密西西比州大学和比勒陀利亚大学，S。非洲）。 AIM 2。通过新方法和图书馆从可培养的微生物中扩展公众可用的化学多样性。 - NPNPD已在FT弗雷德里克校园的NCI上建造，装备和实施了用于高通量培养和微生物的新设施和方法。迪特里克。 - NPNPD通过与俄克拉荷马大学公民科学计划的合同创建了一个在美国收集的13,000个单个土壤真菌的图书馆。 NPNPD已经处理，照片，培养并确定了所有这些样品的序列和分类学。 -NPNPD到目前为止，NCI为保存和分配该资源而登录了100,000个真菌的100,000个单个培养瓶。 - NPNPD已从澳大利亚海洋科学研究所（Australian of Marine Science）完成收购6700个澳大利亚海洋微生物。 - 真菌的原始液体种植，提取和预分级方案已减少为实践。 AIM 3。提供预分级的图书馆，以筛查全球的筛查中心，以加速药物发现。 - 到目前为止，NPNPD已经生产了450,000个预分级提取物，并在28,000 384孔板上镀了18,000,000孔以进行分发。 - NPNPD已向公共的326,000个个人预分级的天然产品样品提供了384孔板。 - 到目前为止，NPNPD运送了4,500,000个筛选样品（在NCI天然产品存储库的前40年历史上，NCI天然产品样品的合并货物还多）。 - 到目前为止，NPNPD已从世界各地的研究组织收到并处理了60项材料转移协议（MTA）的请求，以使这些中心能够筛选NPNPD预分级的天然产品样本。 - NPNPD到目前为止已经完成了30个单独的MTA，并在全球研究机构中完成了研究机构（有关详细列表，请参见附录部分）。 - NPNPD在2018年发表了有关ACS化学生物学特定目的的手稿，这是封面文章。 AIM 4。为研究人员提供高吞吐量筛查支持，以实现目标发现工作。 - NPNPD已与NIAID，NCAT，NCCIH，国防部和英国Astra Zeneca签订了联合研究协议，以使用NPNPD预分级图书馆进行联合药物发现工作。 - NPNPD成功地为CCR Univ的研究人员提供了多个屏幕。德克萨斯州大学。爱荷华州，范德比尔特大学，贝勒医学院，耶鲁医学院，沃尔特·里德陆军研究所，尼亚德和阿斯特拉·塞内卡。 - NPNPD是比勒陀利亚大学（S. Africa）的一项资助的国际研究计划的参与者，该计划将使用NPNPD技术来开发非洲原产地的图书馆，该图书馆将在非洲，澳大利亚，印度，欧洲，欧洲，英国，英国和NCI中放映。 - NPNPD在2020年在自然产品报告中发表了有关此特定目标的手稿，这是封面文章。 AIM 5。提供更快的分析资源（隔离，结构阐明，重新供应），以加快转化管道。 - NPNPD在FT的Frederick校园的NCI上创建，装备和实施了高通量二级纯化和分析化学能力。迪特里克。 - NPNPD创造了每周进行500次净化的能力，每周将10,000个亚划分样品的镀层和干燥。 - NPNPD已成功地使用了CCR/NCI，Astra Zeneca和国防部的多个计划。 - NPNPD生产并运送了25,000个纯化的子部分，这些子部分是从活性NPNPD馏分到筛选中心的25,000个。 - NCI已将这些技术转移到密西西比大学和比勒陀利亚大学，非洲和瑞典。 - NPNPD在2020年发表了有关ACS化学生物学的特定目的的手稿，这是封面文章。目标6。建立一个公共数据库和生物信息学平台，以扩大输入并扩大影响。 - NPNPD正在现代化旧版天然产品数据库中，以将它们带入更现代且易于兼容的数据库结构。这些数据库包括有关分类法，金额，收集位置信息，源生物的照片，史密森尼机构的代金券收集的信息永久性。该协议包括公共访问凭证标本的各个方面。 - NPNPD基于对其生物学活性的分析，开发了自组织的自组织图（SOM）生物信息学系统。 - NPNPD在2021年发表了有关该分子肿瘤学特定目的的手稿，这是封面文章。