Feasibility Studies that Explore Healthy and Diseased Temporomandibular Joints (TMJ) using Single Cell Multi-Omic Analyses (UH2/UH3 Clinical Trial Not Allowed) | RFA DE 22 005

Opportunity Information: Apply for RFA DE 22 005

This National Institutes of Health (NIH) funding opportunity, titled "Feasibility Studies that Explore Healthy and Diseased Temporomandibular Joints (TMJ) using Single Cell Multi-Omic Analyses (UH2/UH3 Clinical Trial Not Allowed)," supports early-stage, exploratory projects aimed at unpacking what is happening inside the temporomandibular joint during health and disease at very high biological resolution. The central scientific focus is temporomandibular joint disorders (TMJD), particularly the cellular and molecular mechanisms that drive pain and tissue dysfunction. The solicitation emphasizes the use of single-cell and related multi-omics approaches, meaning applicants are expected to profile individual cells (and potentially multiple layers of biology such as gene expression, chromatin accessibility, protein markers, or other omics readouts) to better define the cell types, cell states, and pathways involved in TMJD.

A key theme is moving beyond broad tissue-level signals and instead identifying which specific cell populations are present in TMJ-relevant tissues and what those cells are doing in the context of TMJD. The announcement explicitly calls out TMJD target tissues that may be analyzed, including synovial fluid as well as other relevant peripheral tissues such as muscle and skin, recognizing that TMJD pain and dysfunction can involve multiple tissue compartments and not only the joint itself. In addition to studying mechanisms that contribute to disease, the opportunity also encourages work on biological processes associated with resolution, recovery, and homeostasis. In practice, that means applicants can propose studies that contrast healthy versus diseased states, as well as studies that help explain why some individuals improve or maintain stability while others progress.

The desired outcomes are strongly translational in direction, even though the mechanism is for feasibility work rather than a full-scale clinical trial. Projects are expected to generate insights that can support one or more of the following: first, molecular disease classifiers that could be used to stratify patients into biologically meaningful subgroups, which is important in heterogeneous pain conditions like TMJD; second, diagnostic, prognostic, and/or predictive biomarkers derived from cellular signatures or pathway activity, which could help with earlier detection, risk prediction, or treatment selection; and third, identification of novel therapeutic targets, meaning specific cell populations and their effector pathways that could plausibly be modulated to reduce pain, improve tissue function, or promote repair. The overall message is that mapping the single-cell landscape of TMJ-associated tissues should lead to clearer disease definitions and more actionable biology.

Administratively, this is a discretionary NIH opportunity using a cooperative agreement funding instrument (UH2/UH3). Cooperative agreements typically indicate substantial NIH programmatic involvement compared to a standard grant, and the UH2/UH3 structure commonly reflects a phased approach in which an initial, milestone-driven feasibility or start-up phase (UH2) transitions to a second phase (UH3) if milestones are met. The notice specifies "Clinical Trial Not Allowed," meaning applicants should not propose studies that meet NIH’s definition of a clinical trial; instead, the work should remain in the realm of mechanistic, observational, or biospecimen-based human research (or other preclinical/experimental approaches) that do not involve prospectively assigning human participants to interventions to evaluate health-related outcomes.

Eligibility is broad across many U.S.-based organization types. Eligible applicants include state, county, city, township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (excluding institutions of higher education where applicable); for-profit organizations other than small businesses; small businesses; and other categories identified by NIH. The opportunity also highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, eligible federal agencies, Indian/Native American tribal governments other than federally recognized entities, and U.S. territories or possessions. At the same time, there are clear restrictions around foreign involvement: non-domestic (non-U.S.) entities and non-domestic foreign institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by the NIH Grants Policy Statement are not allowed.

The opportunity is identified by Funding Opportunity Number RFA-DE-22-005, and it falls under NIH health-related research areas associated with CFDA numbers 93.121 and 93.313. The original posting date is listed as August 12, 2021, with an original closing date of November 10, 2021. An award ceiling is not specified in the provided source information, and the expected number of awards is not listed. Overall, the grant is positioned to help teams generate high-value feasibility data using single-cell multi-omic strategies that can clarify TMJD biology and set the stage for future, larger-scale mechanistic and translational studies.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Feasibility Studies that Explore Healthy and Diseased Temporomandibular Joints (TMJ) using Single Cell Multi-Omic Analyses (UH2/UH3 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.313.
• This funding opportunity was created on 2021-08-12.
• Applicants must submit their applications by 2021-11-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA DE 22 005

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: