Administration Component The Administrative Core is responsible for setting the overall direction of the NeuroLINCS center and for ensuring that the resources and components of the Center are optimally utilized. The successful development and evolution of the NeuroLINCS center requires strong interactions between the leaders and co-leaders of each Component and of the center as a whole. Hence, the NeuroLINCS Administrative Component plays a vital role in facilitating these interactions. Moreover, the Administrative Component and its personnel provide the necessary administrative and fiscal oversight to ensure that the NeuroLINCS center is run efficiently. The NeuroLINCS center involves 5 principal sites with defined responsibilities of growing, differentiating and generating new induced pluripotent stem cell lines (iPSCs), performing data generation assays on human brain cells made from iPSCs in response to perturbagens, performing basic analyses and developing cell signatures through integrated data analysis .methods, and establish community interactions. An integrated and highly collaborative group of investigators with expertise in stem cell biology, IPS cells, quantitative molecular phenotyping (omics and single cell imaging) and bioinformatics will work closely together to generate significant and highly predictive cell signatures. The PIs of the NeuroLINCS center are Steven Finkbeiner (Gladstone), Ernest Frankel (MIT), Jeffrey Rothstein (JHU), Clive Svendsen (Cedars) and Leslie Thompson (UCI), who will serve as leaders and co-leaders of components. Each Component has identified co-investigators/collaborators/consultants appropriate for the planned scientific investigations. Component leaders and co-leaders will also be active participants in NeuroLINCS consortium working groups as they are developed to address specific issues. Results of the genetic, proteomic and other characterization conducted by consortium labs will provide important feedback for further enhancement of induction and differentiation protocols and related methodologies and it is anticipated that this collaborative and iterative approach will lead to the broadest success for the study. An Evaluation Program within the NeuroLINCS is in place to determine if the programs supported are meeting the needs of the research community, are efficiently managed, and demonstrably effective and annual objectives and milestones.

Public Health Relevance

The NeuroLINCS center will address key roadblocks in biomedical research, with an emphasis on the CNS and neurodegenerative disease. It brings together a unique group of investigators with the expertise to generate highly significant and predictive cell signatures using human iPS cells and their neural cell derivatives. These studies will address disease-specific features versus commonalities across human diseases including ALS, SMA, HD, and PD and define their responses to cellular perturbations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS091046-05
Application #
9560947
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617
Nicolas, Aude (see original citation for additional authors) (2018) Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron 97:1268-1283.e6
Christiansen, Eric M; Yang, Samuel J; Ando, D Michael et al. (2018) In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images. Cell 173:792-803.e19
Keenan, Alexandra B; Jenkins, Sherry L; Jagodnik, Kathleen M et al. (2018) The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. Cell Syst 6:13-24
Köksal, Ali Sinan; Beck, Kirsten; Cronin, Dylan R et al. (2018) Synthesizing Signaling Pathways from Temporal Phosphoproteomic Data. Cell Rep 24:3607-3618
Pereira, Gavin C; Sanchez, Laura; Schaughency, Paul M et al. (2018) Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis. Mob DNA 9:35
Xiong, Yuguang; Soumillon, Magali; Wu, Jie et al. (2017) A Comparison of mRNA Sequencing with Random Primed and 3'-Directed Libraries. Sci Rep 7:14626
HD iPSC Consortium (2017) Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice. Nat Neurosci 20:648-660
Akhmedov, Murodzhon; Kedaigle, Amanda; Chong, Renan Escalante et al. (2017) PCSF: An R-package for network-based interpretation of high-throughput data. PLoS Comput Biol 13:e1005694
Grima, Jonathan C; Daigle, J Gavin; Arbez, Nicolas et al. (2017) Mutant Huntingtin Disrupts the Nuclear Pore Complex. Neuron 94:93-107.e6
Gendron, Tania F; Chew, Jeannie; Stankowski, Jeannette N et al. (2017) Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Sci Transl Med 9:

Showing the most recent 10 out of 27 publications