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

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

What is the official title of this NIH funding opportunity?

The opportunity is titled "New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)."

What is the Funding Opportunity Number (FON) and CFDA listing?

The Funding Opportunity Number is RFA-RM-20-006, and the CFDA number listed is 93.310.

Which agency is offering this grant?

This opportunity is offered by the National Institutes of Health (NIH).

What is the main scientific focus of this announcement?

It supports research on how the genome is organized and functions in space and time, commonly described as the "4D nucleome" (3D genome organization plus changes over time), and how those 4DN features relate to human health and disease.

Who is the intended applicant investigator audience?

The solicitation supports projects led by NIH-defined New Investigators who are establishing or advancing independent research programs related to 4DN organization and function.

What type of award mechanism is used?

Awards are made as a U01 cooperative agreement.

What does a U01 cooperative agreement imply for how the project is run?

A U01 cooperative agreement typically includes substantial programmatic involvement by NIH staff during the project, in addition to providing funding.

Are clinical trials allowed under this opportunity?

No. The notice states "Clinical Trial Not Allowed," meaning proposed studies must not meet NIH's definition of a clinical trial.

If clinical trials are not allowed, what kinds of studies does NIH appear to be aiming for?

The description emphasizes mechanistic, translational, or preclinical research that monitors and/or manipulates 4DN features and connects those changes to meaningful outcomes in human health and disease, without prospectively assigning human participants to interventions to evaluate health-related outcomes.

Does the announcement require a specific disease area?

No. Applicants may propose work in any human disease area or biological process consistent with NIH's broad mission, rather than being limited to a narrow disease category.

What is meant by connecting 4DN organization to "real biological and biomedical outcomes"?

The opportunity emphasizes projects that link 4DN organization and dynamics to functional consequences relevant to biology and biomedicine, rather than treating genome architecture as a stand-alone descriptive endpoint.

What kinds of tools or approaches are encouraged?

Applicants are encouraged to use either newly developed or already-established experimental and computational tools to monitor and/or intentionally manipulate 4DN features, and then relate those changes to health- or disease-relevant questions.

Is manipulating 4DN features required?

The announcement encourages projects that, where possible, test cause-and-effect by manipulating 4DN features and measuring downstream functional consequences.

How important is time to the proposed research design?

Time is treated as a first-class variable. NIH is looking for studies designed to capture and interpret changes in nuclear organization over relevant timescales, rather than a single snapshot of genome architecture.

What time-based biological contexts are explicitly mentioned as examples?

Examples include development and lifespan changes (early development, adulthood, aging, disease progression) and shorter or recurring timeframes such as circadian rhythms, fasting/feeding cycles, reproductive cycles, and sleep/wake cycles.

Are studies of environmental exposures within scope?

Yes. 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.

Can projects focus on changes across development or aging?

Yes. The opportunity invites projects examining how 4DN patterns evolve across development and the full lifespan, including stages such as early development, adulthood, aging, and disease progression.

Are applicants expected to study 4DN only in humans?

The opportunity is centered on human health and disease, and it notes that researchers can often use systems such as 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.

Can a project include human biospecimens or human-derived model systems?

Yes. The description indicates that using human biospecimens, cell lines, and organoids can be appropriate, provided the study does not meet NIH's definition of a clinical trial.

What is the maximum award amount indicated in the opportunity details?

The listed award ceiling is $400,000, indicating the maximum amount expected per award within the parameters of this funding announcement.

How is this opportunity categorized in the provided details?

It is categorized as discretionary funding, with the activity category listed as Health.

When was the opportunity created and what was the original application closing date?

The opportunity was created on 2019-11-25 and had an original application closing date of 2020-03-02.

What types of organizations are eligible to apply?

Eligible applicants include a broad range of organizations, including various levels of U.S. government (state, county, city, township, special district), 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.

Which specific institution types are explicitly welcomed?

The announcement highlights and welcomes applications from Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, TCCUs, faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

Are tribal governments that are not federally recognized eligible?

Yes. The information notes that Indian/Native American Tribal Governments that are not federally recognized are included among other eligible applicant types.

Can a non-U.S. (foreign) institution apply as the main applicant?

No. Non-domestic (non-U.S.) entities are not eligible to apply as the applicant organization.

Are non-domestic components of U.S. organizations eligible to apply?

No. Non-domestic components of U.S. organizations are not eligible to apply as the applicant organization.

Are foreign components allowed in a project led by a U.S. applicant?

Yes. "Foreign components" are allowed as defined by the NIH Grants Policy Statement, meaning a U.S.-based applicant may include scientifically justified elements of the work conducted outside the U.S. under NIH foreign component rules, even though a foreign institution cannot be the primary applicant.

What overall outcomes is NIH trying to drive with this solicitation?

The solicitation is designed to help new investigators establish independent research programs that clarify how changes in nuclear genome organization contribute to human health, disease mechanisms, and responses to environmental or physiological exposures.