Epitranscriptomics Crosstalks and Toxicants (EPCOT) (R01 Clinical Trials Not Allowed) | RFA ES 25 001

Opportunity Information: Apply for RFA ES 25 001

The Epitranscriptomics Crosstalks and Toxicants (EPCOT) funding opportunity (RFA-ES-25-001) is a National Institutes of Health (NIH) discretionary grant solicitation that will support new R01 research projects focused on the biological mechanisms linking environmental toxicant exposures to changes in epitranscriptomic regulation and, ultimately, to adverse health outcomes. The core goal is to encourage innovative, mechanistic studies that explain how toxicants can inhibit normal epitranscriptomic interactions, trigger new (aberrant) interactions, or otherwise reshape these regulatory networks in ways that contribute to the initiation, progression, or worsening of disease and other negative health effects. Clinical trials are not allowed under this announcement, so the emphasis is on basic, mechanistic, and translational research that does not involve testing clinical interventions in humans.

A central concept in this opportunity is "epitranscriptomic crosstalks." In this context, crosstalk refers to the interplay among (1) epitranscriptomic marks on RNA (chemical modifications that influence RNA fate and function), (2) the protein machinery that interacts with those marks, and (3) other layers of genomic regulation and structure. The solicitation specifically defines epitranscriptomic crosstalks as interactions between epitranscriptomic marks and their associated Readers, Writers, and Erasers (often abbreviated as RWEs), alongside interactions with epigenomic marks and/or epigenomic RWEs and broader genomic structures. In practical terms, this means applicants are expected to go beyond simply cataloging RNA modifications after exposure and instead interrogate how toxicants alter multi-layer regulatory relationships, such as how RNA modifications and their binding proteins intersect with chromatin marks, DNA-associated regulation, and higher-order genome organization to influence gene expression programs and cellular phenotypes relevant to health.

Projects proposed to EPCOT should be designed to deliver mechanistic insight. The intent is not merely observational association (for example, noting that a toxicant changes an RNA modification level), but rather explanatory work that clarifies causal pathways and biological consequences, such as identifying which RWEs are affected, how those perturbations propagate across epigenomic or genomic regulatory systems, and how those linked disruptions drive toxicity-relevant endpoints. The health framing is broad: the announcement explicitly includes mechanisms tied to the onset of adverse outcomes, their progression over time, and the exacerbation of existing conditions, which creates room for proposals spanning early molecular initiating events through downstream pathophysiology.

From an administrative and eligibility standpoint, EPCOT uses the NIH R01 grant mechanism. The opportunity is categorized under Environment and Health (CFDA 93.113). The application due date listed is February 6, 2025. The award ceiling is noted as $500,000, indicating an upper bound on the amount that can be requested under the terms summarized here. The posting indicates expected awards but does not provide a specific number in the provided text.

A wide range of domestic applicant organizations are eligible, reflecting NIH's broad participation model. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized governments; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The opportunity also explicitly highlights additional eligible applicant types, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

Foreign eligibility is constrained in a way that is common for many NIH opportunities. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply as the primary applicant organization. However, non-domestic components of U.S. organizations are eligible to apply, and foreign components (as defined in the NIH Grants Policy Statement) are allowed. In effect, a U.S.-based applicant can include certain foreign collaborations or components when justified, but a foreign institution cannot serve as the applicant organization submitting the R01 as the prime recipient.

Overall, EPCOT is aimed at pushing the field toward a more integrated understanding of how environmental exposures reshape RNA-centered regulation in coordination with epigenomic and genomic systems, and how those coordinated disruptions translate into harmful biological outcomes. The strongest applications will likely be those that clearly define the epitranscriptomic crosstalk being studied, connect toxicant exposure to specific molecular perturbations in RWEs and interacting regulatory layers, and map those perturbations to mechanistic pathways that plausibly explain adverse health effects without proposing a clinical trial.

• The National Institutes of Health in the environment, health sector is offering a public funding opportunity titled "Epitranscriptomics Crosstalks and Toxicants (EPCOT) (R01 Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.113.
• This funding opportunity was created on 2024-11-14.
• Applicants must submit their applications by 2025-02-06. (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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