PD iPS Cell Line Consortium

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-赠款”工作的延续，我们的9个研究小组现在提出了一个U24赠款财团。用于帕金森病（PD）患者来源的IPS细胞系的公共和科学用途的工具生成将继续进行，具有突变的新系，等基因遗传修复的iPS系，以及用于研究这些系的报告系统的插入物将由U赠款提供的资金建立。PD iPS联盟主任Ole Isacson博士和由核心领导人、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 Wszoiek领导的临床和遗传核心，将提供必要的患者成纤维细胞系，包括GBA、FTD和其他LRRK 2和α突触核蛋白突变，沿着一个mRNA测序和表达实验室。这些细胞系将根据RFA设定的优先级进行重新编程，（2）在iPS核心设施的哈佛干细胞研究所与其主任Rossi和科万博士以及纽约干细胞基金会（NYSCF）与主任Scott Noggle博士签订合同，及时提供新细胞系。（3）重编程，分化报告（和等基因修复）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PINK 1和LRRK 2 G2019 S基因修复为其等基因形式，并将荧光报告基因添加到这些PD iPS细胞中。这些工具和试剂将使由Ted Dawson领导的（4）细胞功能和病理生理学核心的任务成为可能，他将指导围绕PD的表型和病因生物学发现的团队合作。该U24资助提案提供的价值通过以下方式实现：（a）提供新的iPS系，和（B）工程化PD IPS系作为理解PD的非常有用的人类细胞工具，以及（c）用于药物发现的细胞系的协作和共享使用。 公共卫生相关性：将从与帕金森病（PD）相关的独特基因突变中开发工具，以提供具有工程修复和报告功能的新PD iPS细胞，这些细胞可供全球科学团队用于对PD病因学进行重大发现。这种新的人类细胞系由公共/私人伙伴关系可以提供加速工作的新疗法PD通过允许特定的和独特的人类细胞测定。

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.