Key Dates

Related Announcements

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

Issued by

National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The Alzheimer's Disease Related Dementias (ADRD) Summits (convened by the NINDS in 2013, 2016, and 2019) recommend the collection of source cells and induced pluripotent stem cell (iPSC) lines from patients with ADRDs (Frontotemporal Dementia (FTD), Lewy Body Dementia (LBD), Vascular contributions to Cognitive Impairment and Dementia (VCID), and Multiple Etiology Dementias). Along with linked de-identified clinical data, these resources are to be shared broadly with the scientific research community by both NIH funded researchers, by the ADRD research community at large, and through the NINDS Human Cell and Data Repository (NHCDR) - an NINDS funded repository that serves as a resource to both academic and industry investigators to advance basic and translational research in neurological disorders.

The purpose of this Notice of Special Interest (NOSI) is to encourage submission of applications for administrative supplements to provide deep quality control and molecular phenotyping of ADRD iPSC lines to enable the study of how genetic variants influence on convergent ADRD disease pathways. The funds from these Administrative Supplements are intended to support research activities on existing ADRD iPSCs (including isogenic control and edited lines) and their source cell lines including: (1) Whole Genome Sequencing (WGS), (2) RNA-Sequencing (RNA-seq) and (3) DNA methylation profiling. WGS will be used to identify the fraction of variability derived from the genetic background of the iPSC lines. Transcriptomic and methylation profiling will provide additional insight into drivers of iPSC variability such as epigenetic state and determine whether somatic mutations occurring during reprogramming have functional consequences in gene expression patterns. The generation of systematically derived ADRD iPSC resources associated with well-characterized and standardized genomic, transcriptomic and epigenomic profiling will aid in validating the quality and integrity of the cell lines as well provide a vital resource in interrogating the genetic contribution to underlying ADRD disease mechanisms.

Eligibility

Only supplement applications to parent awards that have an NS designation for NIH institute and are active (i.e., not in a no-cost or funded extension) are eligible for support under this NOSI.

Administrative supplement requests are sought from NINDS awardees that have:

• Researchers who have previously contributed source cells and/or iPSCs from subjects with ADRDs to the NHCDR
• Researchers who have never contributed source cells and/or iPSCs from subjects with ADRDs to the NHCDR, but can meet the following requirements in accordance with NOT-NS-14-032 including:
  • Source cells and iPSC lines must be deposited into NHCDR- a timeline for sharing must be provided;
  • Patient consent must allow for de-identified and broad data and resource sharing (academic and industry investigators) including use for genetic studies, wherein part or all of the genome may be sequenced;
  • When IP is applicable, the institution/facility must have all necessary legal authority for sharing, and document this, including any necessary licenses for iPSC and related (e.g. genome editing, reporter use) technologies that allow deposition and broad distribution of resulting iPSC lines through the NINDS Repository;
  • All iPSC lines derived under NINDS funding mechanisms must be characterized for sterility and be free of mycoplasma contamination, have normal karyotypes, normal growth rates and colony morphology, demonstrated pluripotency through a pluritest, scorecard test or equivalent test, demonstrate surface antigen expression of stem cell markers, demonstrated ability to form embryoid bodies and demonstrated transgene silencing for the reprogramming factors used 

All sequence data and associated clinical and phenotypic data will be deposited to an appropriate NIH designated data repository, such as dbGaP, in coordination with NINDS Program staff.

Due to the unique requirements of this project, applicants are strongly encouraged to consult with NINDS Scientific/Research Staff during the planning for an application.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.

• PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

• Application Due Date(s) – May 5, 2021, by 5:00 PM local time of applicant organization.
• For funding consideration, applicants must include “NOT-NS-21-041” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
• Requests may be for one year of support only.
• The Research Strategy section of the application is limited to 6 pages.
• Application budgets must reflect the actual needs of the proposed project. Supplement budget requests may not exceed $666,000 per year in direct costs or 100% of the direct costs of the current year of the parent award (exclusive of Facilities and Administrative costs on sub-contracts), whichever is lower. Applications that want to propose higher budgets must receive permission from the project officer and IC Contact prior to submission.
• The application Abstract section should describe the proposed supplement, and the Research Strategy section should include a summary or abstract of the funded parent award or project. The Research Strategy should state the relevance to the parent award and AD/ADRD, and articulate the component(s) and any IC-specific priorities that the supplement is addressing.
• Applicants are strongly encouraged to notify the program contact at the Institute supporting the parent award that a request has been submitted in response to this FOA in order to facilitate efficient processing of the request.
• Only electronic submissions will be accepted for this funding opportunity. Use one of the methods described in PA-20-272.
• The parent award must be active (i.e., not in a no-cost or funded extension) when the supplemental application is submitted regardless of the time remaining on the current project.

Inquiries

Please direct all inquiries to:

Dr. Christine Swanson-Fischer, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: christine.swanson-fischer@nih.gov