Background

While considerable progress has been made in associating genetic variants with common and rare DOC diseases and conditions, knowledge is not yet complete about genes involved and genetic variation, heterogeneity, penetrance, and expressivity. In addition, functional characterization and mechanistic studies of DOC genes and variants have not yet been carried out fully to gain a better understanding of DOC biology and disease etiology.

Specific Areas of Research Interest

This Notice calls for research projects targeting human DOC phenotypes that propose specific aims in each of the following categories: 1) discovery of candidate causal genetic variants, 2) functional characterization of identified variants, and 3) mechanistic studies.

1. Applicants should propose genome-wide (whole exome, whole genome, or transcriptome) sequencing and analysis of human study participants, aiming for discovery of novel DOC variants or novel phenotypes previously not associated with any known DOC variant, with or without complementary omics approaches including genotyping.
2. Applicants should propose characterization of functional significance/consequences of identified human candidate genes/variants using animal models, in vitro systems, in silico methods, or other approaches.
3. Concurrent with functional characterization, or under a separate aim, applicants should propose experimental and/or analytical work that can shed light on mechanistic aspects of disease etiology.

Work proposed must be well-justified with strong scientific rational and consideration of costs. For example, whole genome sequencing and analysis, rather than whole exome sequencing and analysis, as the main or sole approach for discovery of candidate causal variants, must be well-justified.

While an applicant can request funds for all proposed aims, he/she is highly encouraged to capitalize on existing resources for the proposed project to reduce costs and integrate all necessary expertise. Examples include, but are not limited to:

1. A project that analyzes existing sequencing and phenotypic data for the variant discovery aim, while requesting funds for follow-up phenotyping and sequencing of a subset of study participants.
2. A project that sequences and analyzes existing and well-phenotyped study participants for the variant discovery aim. If necessary, the project can request funds for additional and well-designed recruitment and/or phenotyping of existing and/or new participants.
3. A project that teams up with a research group that seeks research collaboration and offers sequence production and analysis at no cost to the new project.
4. A project that collaborates with an existing program for functional characterization of candidate causal variants.

Application and Submission Information

This notice applies to due dates on or after January 7, 2020 and subsequent receipt dates through January 8th, 2022 .

Submit applications for this initiative using the following funding opportunity announcement (FOA) or any reissues of these announcement through the expiration date of this notice.

• PA-19-056 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-DE-19-016 (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.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Lu Wang, Ph.D.
National Institute of Dental and Craniofacial Research
Telephone: 301-594-4846
Email: wanglu@nidcr.nih.gov

Kathryn Stein, Ph.D.
National Institute of Dental and Craniofacial Research
Telephone: 301-827-4653
Email: kathryn.stein@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov