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-grant”工作的延续，我们的9个研究团队现在提议成立一个U24资助联盟。将继续为公众和科学使用帕金森氏症（PD）患者衍生的诱导多能干细胞系开发工具，并将利用U基金提供的资金建立具有突变的新细胞系、等基因修复的诱导多能干细胞系以及用于研究这些细胞系的报告系统的插入。PD iPS联盟主任Ole Isacson博士和由核心领导、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。这些线路将根据RFA在哈佛干细胞研究所（Harvard Stem Cell Institute）的(2)个合同研究组织（cro）确定的优先级重新编程。罗西和考恩，以及纽约干细胞基金会（NYSCF）主任斯科特·诺格尔博士，及时提供了新的细胞系。(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一个强大的分化方案，并将PINK1和LRRK2 G2019S基因修复为等基因形式，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Ted Dawson领导的细胞功能和病理生理学核心(4)的分配成为可能，他将指导围绕PD的表型和病因生物学发现的团队合作。U24资助提案提供的价值体现在(a)提供新的iPS系，(b)工程PD iPS系作为理解PD的非常有用的人类细胞工具，以及(c)协作和共享细胞系用于药物发现。

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.