PD iPS Cell Line Consortium

PD iPS 细胞系联盟

• 批准号: 8288421
• 负责人: OLE ISACSON
• 金额: $ 92.07万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288421
• 关键词: Applications Grants; Biological Assay; Cell Line; Cell physiology; Cells; Cellular Assay; Clinical; Clone Cells; Core Facility; Deposition; Disease; Engineering; Etiology; Fibroblasts; Foundations; Frontotemporal Dementia; Functional disorder; Funding; Gene Mutation; Generations; Genetic; Grant; Human; Human Cell Line; Individual; Institutes; LRRK2 gene; Laboratories; Messenger RNA; Mutation; New York; PINK1 gene; Parkinson Disease; Parkinsonian Disorders; Patients; Phenotype; Protocols documentation; Reagent; Recruitment Activity; Reporter; Reporter Genes; Research; Research Contracts; Resources; Sampling; Science; Stem cells; Structure; System; United States National Institutes of Health; Work; alpha synuclein; biobank; dopaminergic neuron; drug discovery; induced pluripotent stem cell; public-private partnership; repaired; tool

DESCRIPTION (provided by applicant): As a continuation of the NIH-funded "GO-grant" work on PD IPS cell genetic lines our 9 research teams are now proposing a U24 grant consortium, according to the new RFA NS-11-011. The tool generation for public and scientific use of Parkinson's disease (PD) patient derived IPS cell lines will continue and new lines with mutations, isogenic genetically repaired iPS lines, and inserts of reporter systems for studying such lines will be established by the funds provided by the U grant. The PD iPS consortium director, Dr. Ole Isacson, and the Executive Science Committee consisting of Core leaders, the IPS resource representative and an NIH representative will carry out the work through the activity of: the (1) Clinical and Genetic Core led by Zbigniew Wszoiek that will provide necessary patient fibroblast lines, including GBA, FTD and additional LRRK2 and alpha synuclein mutations, along with a mRNA sequencing and expression laboratory. These lines will be reprogrammed according to the priorities set by the RFA at (2) contracting research organizations (CROs) at the Harvard Stem Cell Institute with their Directors Drs. Rossi and Cowan at the iPS Core facility, and the New York Stem Cell Foundation (NYSCF) with the Director Dr. Scott Noggle, providing the new lines in a timely manner. The (3) Reprogramming, Differentiation Reporter (and Isogenic Repair) Core is led by Lorenz Studer and Dimitri Krainc, who will provide a robust differentiation protocol for dopamine neurons and genetically repair PINK1 and LRRK2 G2019S into their isogenic forms and also add fluorescent reporter genes to these PD iPS cells. These tools and reagents will enable the assignments of the (4) Cell Function and Pathophysiology Core led by Ted Dawson, who will direct the teamwork around the phenotypes and etiobiology discovery of PD. The value provided by this U24 grant proposal is realized by the (a) new iPS lines provided, and (b) the engineered PD IPS lines as exceptionally useful human cellular tools for understanding PD, as well as (c) collaborative and shared use of cells lines for drug discovery. PUBLIC HEALTH RELEVANCE: Tools will be developed from unique genetic mutations associated with Parkinson's disease (PD) to provide new PD iPS cells with engineered repair and reporter features that can be used by scientific teams worldwide to make significant discoveries about the etiology of PD. Such new human cell lines by public/private partnerships can provide accelerated work on new treatments for PD by allowing specific and unique human cellular assays.

描述（由申请人提供）：根据新的 RFA NS-11-011，作为 NIH 资助的 PD IPS 细胞遗传系“GO 资助”工作的延续，我们的 9 个研究团队现在提议建立一个 U24 资助联盟。将继续开发用于帕金森病 (PD) 患者衍生的 IPS 细胞系的公共和科学用途的工具，并且将由以下机构提供的资金建立带有突变的新细胞系、同基因基因修复的 iPS 细胞系以及用于研究此类细胞系的报告系统插入物。大学补助金。 PD iPS 联盟主任 Ole Isacson 博士以及由核心领导人、IPS 资源代表和 NIH 代表组成的执行科学委员会将通过以下活动开展工作： (1) 由 Zbigniew 领导的临床和遗传核心Wszoiek 将提供必要的患者成纤维细胞系，包括 GBA、FTD 和额外的 LRRK2 和 α 突触核蛋白突变，以及 mRNA 测序和表达实验室。这些细胞系将根据 RFA 在哈佛干细胞研究所的 (2) 个合同研究组织 (CRO) 及其主任 Drs. 设定的优先级进行重新编程。 iPS Core 设施的 Rossi 和 Cowan 以及纽约干细胞基金会 (NYSCF) 与总监 Scott Noggle 博士一起及时提供了新细胞系。 (3) 重编程、分化报告基因（和同基因修复）核心由 Lorenz Studer 和 Dimitri Krainc 领导，他们将为多巴胺神经元提供强大的分化方案，并将 PINK1 和 LRRK2 G2019S 基因修复为其同基因形式，并添加荧光报告基因这些 PD iPS 细胞。这些工具和试剂将支持由 Ted Dawson 领导的 (4) 细胞功能和病理生理学核心的分配，他将围绕 PD 的表型和病因生物学发现指导团队合作。这项 U24 拨款提案提供的价值是通过以下方式实现的：(a) 提供的新 iPS 系，以及 (b) 工程化的 PD IPS 系作为理解 PD 的特别有用的人类细胞工具，以及 (c) 协作和共享使用用于药物发现的细胞系。 公共健康相关性：将从与帕金森病 (PD) 相关的独特基因突变开发工具，为新的帕金森病 iPS 细胞提供工程修复和报告功能，全世界的科学团队可以使用这些细胞来对帕金森病的病因学做出重大发现。公共/私人合作伙伴关系的此类新人类细胞系可以通过允许特定和独特的人类细胞测定来加速帕金森病新疗法的工作。