New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed) | RFA RM 20 006

Opportunity Information: Apply for RFA RM 20 006

The National Institutes of Health (NIH) grant opportunity "New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-RM-20-006; CFDA 93.310) supports research projects led by NIH-defined New Investigators who want to study how the genome is organized and functions in space and time, often described as the "4D nucleome" (3D genome organization plus changes over time). The goal is to encourage early-stage, independent investigators to use either new or already-established experimental and computational tools to monitor and/or intentionally manipulate 4DN features, and then connect those 4DN changes to meaningful questions in human health and disease. Awards are made as a U01 cooperative agreement, which typically means NIH staff will have substantial programmatic involvement during the project in addition to providing funding.

A central emphasis of this opportunity is linking 4DN organization and dynamics to real biological and biomedical outcomes. Applicants can propose work on any human disease area or biological process that fits within NIH's broad mission, rather than being limited to a narrow disease category. The announcement explicitly welcomes studies focused on environmental exposures and other external influences that may reshape genome organization, including addictive substances, toxins, and psychosocial stress. It also invites projects that examine how 4DN patterns evolve across development and the full lifespan, recognizing that genome architecture and gene regulation can shift across stages like early development, adulthood, aging, and disease progression.

Time is treated as a first-class variable in the science encouraged here. Beyond long-term trajectories across the lifespan, the opportunity points to shorter and recurring biological timeframes that can be used to probe dynamic genome organization. Examples include circadian rhythms, fasting and feeding cycles, reproductive cycles, and sleep/wake cycles. In practice, this means NIH is looking for projects that do more than take a single snapshot of genome architecture; they want studies designed to capture and interpret changes in nuclear organization over relevant timescales, and ideally to test cause-and-effect by manipulating 4DN features and measuring downstream functional consequences.

The funding instrument is a cooperative agreement (U01) and the notice states "Clinical Trial Not Allowed," meaning proposed studies must not meet NIH's definition of a clinical trial. In general terms, the work should remain in the realm of mechanistic, translational, or preclinical research rather than prospectively assigning human participants to interventions to evaluate health-related outcomes. Researchers can still often use human biospecimens, cell lines, organoids, animal models, and other systems to investigate human biology and disease mechanisms, as long as the proposed aims do not constitute a clinical trial under NIH rules.

Eligible applicants cover a wide range of organization types, reflecting NIH's intent to support a broad research community. This includes state, county, city, township, and special district governments; federally recognized Native American tribal governments; public housing authorities/Indian housing authorities; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits with or without 501(c)(3) status (excluding institutions of higher education where specified); for-profit organizations (other than small businesses) as well as small businesses; and other eligible entities. The announcement also highlights specific categories of organizations that are explicitly welcomed, including 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, eligible federal agencies, regional organizations, and U.S. territories or possessions. It also notes that Indian/Native American Tribal Governments that are not federally recognized are included among other eligible applicant types.

There are important limits related to foreign participation. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply as the applicant organization. However, "foreign components" are allowed as defined by the NIH Grants Policy Statement, which generally means a U.S.-based applicant can include certain scientifically justified elements of work being conducted outside the U.S. under NIH's foreign component rules, even though a foreign institution cannot be the primary applicant.

From the administrative details provided, the opportunity was created on 2019-11-25 and had an original application closing date of 2020-03-02. The listed award ceiling is $400,000, indicating the maximum amount expected per award within the parameters of this funding announcement. The opportunity falls under the NIH and is categorized as discretionary funding, with the activity category listed as Health.

Overall, this solicitation is designed to help new investigators establish independent research programs at the intersection of genome architecture, nuclear organization, and disease-relevant function. Competitive projects under this call would be expected to combine strong, well-justified biomedical questions with rigorous approaches for measuring 4DN structure and dynamics (and, where possible, manipulating them) across meaningful timeframes or conditions, ultimately clarifying how changes in nuclear genome organization contribute to human health, disease mechanisms, and responses to environmental or physiological exposures.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 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): 93.310.
• This funding opportunity was created on 2019-11-25.
• Applicants must submit their applications by 2020-03-02. (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 $400,000.00 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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