Research Tools for Difficult to Culture Eukaryotic Pathogens (R61/R33 Clinical Trial Not Allowed) | RFA AI 23 055

Opportunity Information: Apply for RFA AI 23 055

The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Research Tools for Difficult to Culture Eukaryotic Pathogens (R61/R33 Clinical Trial Not Allowed)" under funding opportunity number RFA-AI-23-055 (CFDA 93.855). The program is focused on advancing basic and enabling research capabilities for a small set of human eukaryotic pathogens that are notoriously hard to grow or manipulate in the lab. Specifically, it targets the microsporidian Enterocytozoon bieneusi, Pneumocystis jirovecii, Plasmodium vivax, and Babesia microti. The central idea is to fund ambitious, higher-risk projects that can remove technical bottlenecks by creating reliable culture systems and/or new genetic and molecular tools, so researchers can more effectively study pathogen biology and, downstream, support better diagnostics, therapeutics, and preventive strategies.

A major feature of this opportunity is its milestone-driven, two-phase award structure using the R61/R33 mechanism. The first phase (R61) is intended for early, proof-of-concept work where teams take on challenging development tasks with clear, objective milestones. The second phase (R33) is not automatic; it is only available if the project successfully meets the predefined R61 milestones. In practical terms, applicants need to propose a development plan that is tightly organized around measurable outputs and decision points, because the transition to the R33 depends on demonstrating that the approach is working well enough to justify expansion, optimization, and broader application. This structure is designed to support bold tool-building efforts while still holding projects accountable to concrete progress.

The scientific scope emphasizes development of "robust culture techniques" and "genetic and molecular tools." Culture techniques could include improved in vitro propagation methods, host-cell or organoid-based culture platforms, optimized media and growth conditions, or other reproducible systems that allow sustained growth, life-cycle progression, or experimental access to stages that are currently inaccessible. Genetic and molecular tools could include methods for genome editing, transfection, stable or transient expression systems, selectable markers, reporter strains, single-cell or spatial approaches tailored to these organisms, and standardized assays that make experiments reliable and comparable across labs. The overarching goal is not simply incremental optimization, but the creation of enabling technologies that meaningfully expand what is experimentally possible for these pathogens.

The NOFO explicitly states that clinical trials are not allowed, which signals that the funded work should remain in the realm of tool and method development and foundational pathogen biology rather than interventional studies in human participants. Projects should therefore be framed around laboratory, preclinical, and technology-development objectives, with success defined by technical performance, reproducibility, and usefulness to the wider research community.

Eligibility is broad and includes many types of domestic U.S. organizations: state, county, and local governments; special district governments; independent school districts; public and state-controlled universities; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside of higher education); for-profit organizations (other than small businesses); and small businesses. In addition, the NOFO highlights other eligible applicants such as 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, non-U.S. entities (foreign organizations), regional organizations, Indian/Native American Tribal Governments other than federally recognized entities, and U.S. territories or possessions. This wide eligibility is meant to encourage participation from diverse institutions and to tap expertise wherever it exists, including internationally, which can be particularly relevant for pathogens with geographic or epidemiologic concentrations outside the continental U.S.

Key administrative details include an original application closing date of February 2, 2024, a listed award ceiling of $250,000, and an NIH posting/creation date of August 30, 2023. While the entry does not specify the number of expected awards, the combination of a defined ceiling and the milestone-gated R61/R33 structure suggests an emphasis on targeted, carefully managed investments in tool development rather than large, open-ended research programs.

Overall, this opportunity is best understood as NIH support for the kind of foundational, technical breakthroughs that can unlock an entire field. By prioritizing hard-to-culture eukaryotic pathogens and insisting on milestone-based progress, the program aims to accelerate the development of reliable lab systems and molecular toolkits that will let researchers ask questions that are currently out of reach, and to do so in a way that is reproducible and broadly usable by the scientific community.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Research Tools for Difficult to Culture Eukaryotic Pathogens (R61/R33 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): 93.855.
• This funding opportunity was created on 2023-08-30.
• Applicants must submit their applications by 2024-02-02. (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 $250,000.00 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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