Exploring Proteogenomic Approaches to Unravel the Mechanisms of Mis-Folded Protein Accumulation in Tauopathies (R01 Clinical Trial Not Allowed) | RFA AG 25 017

Opportunity Information: Apply for RFA AG 25 017

Exploring Proteogenomic Approaches to Unravel the Mechanisms of Mis-Folded Protein Accumulation in Tauopathies (R01 Clinical Trial Not Allowed) is a National Institutes of Health (NIH) grant opportunity (RFA-AG-25-017) that supports research aimed at understanding how misprocessed and misfolded proteins accumulate in tauopathies, including in the context of aging, Alzheimer’s disease (AD), and Alzheimer’s disease-related dementias (ADRD). The core scientific emphasis is on pinpointing where and how these abnormal protein processes unfold at a much finer resolution than traditional bulk tissue studies can provide, specifically focusing on distinct brain regions and specific cell types. By framing the problem around region- and cell-type specificity, the opportunity seeks to move beyond generalized descriptions of pathology and toward clearer, mechanistic explanations of why certain neuronal populations are vulnerable and what biological consequences follow as proteostasis (protein homeostasis) breaks down over time.

A central priority of this opportunity is the development and application of next-generation proteogenomic approaches at the single-cell level or within purified single-cell types. In practical terms, this means building or improving platforms that can capture coordinated changes across protein measurements (proteomics) and genome-wide molecular readouts (often transcriptomics and related “omics”) in the same cell or cell type, with enough sensitivity to detect dynamic stress and protein-misfolding responses. The NIH explicitly encourages collaborative team science to bring together the expertise needed to create these advanced tools, which often require a mix of neurobiology, mass spectrometry-based proteomics, genomics, computational biology, and method development. The intention is that these platforms will help map how neuronal proteomes respond to misfolding stress across aging and disease progression, and how those responses might contribute to downstream dysfunction or degeneration.

The work supported by this announcement is positioned to clarify both the molecular signatures and the functional consequences of protein misprocessing and misfolding in tauopathy-relevant contexts. Projects are expected to generate insights into the changing landscape of misfolding responses over time, potentially identifying cellular pathways that fail (or compensate) during aging, and revealing how those shifts relate to AD/ADRD development. While the description is technology-forward, the ultimate goal is biological understanding: explaining the mechanisms that drive selective vulnerability and linking proteome-level disruptions to meaningful outcomes in neurons and other brain cell types implicated in tauopathy.

From an administrative standpoint, this is an R01 research project grant mechanism under the NIH, categorized as discretionary funding and aligned with a health funding activity area. Clinical trials are not allowed under this announcement, indicating that the funded studies should be preclinical, mechanistic, or methods-focused rather than interventional studies evaluating clinical outcomes in human participants. The opportunity was created on March 13, 2024, and the original application closing date was June 10, 2024. The listed award ceiling is $500,000, and the opportunity notes expected awards but does not provide a specific number in the source data provided.

Eligibility is broad and includes many types of organizations that can contribute to this kind of multidisciplinary science. Eligible applicants include state, county, city or township governments; 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; other Native American tribal organizations; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations (other than small businesses); small businesses; and other eligible entities. The announcement also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, eligible federal agencies, Indian/Native American Tribal Governments that are not federally recognized, and non-domestic (non-U.S.) entities (foreign organizations). This breadth signals an intent to encourage wide participation, including institutions serving underrepresented communities and international partners capable of contributing specialized expertise.

Overall, the opportunity is aimed at accelerating progress in tauopathy research by funding projects that combine strong mechanistic questions with powerful single-cell or single-cell-type proteogenomic technologies. The NIH is essentially looking for proposals that can reveal, with cell-level precision, how misfolded and misprocessed proteins build up in tauopathies, how neurons and other brain cells respond to that stress over aging, and what those responses mean for the onset and progression of AD and ADRD.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Exploring Proteogenomic Approaches to Unravel the Mechanisms of Mis-Folded Protein Accumulation in Tauopathies (R01 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): 93.866.
• This funding opportunity was created on 2024-03-13.
• Applicants must submit their applications by 2024-06-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• 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.

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