Generating New Insights and Mechanistic Understanding of Antibiotic Resistance Development (R21 Clinical Trial Not Allowed) | PA 18 724

Opportunity Information: Apply for PA 18 724

Generating New Insights and Mechanistic Understanding of Antibiotic Resistance Development (R21 Clinical Trial Not Allowed) is a National Institutes of Health (NIH) discretionary grant opportunity (Funding Opportunity Number PA 18-724; CFDA 93.855) designed to support early-stage, exploratory research that can uncover new biological insights into how antibiotic resistance develops and spreads. The announcement is aligned with priorities in the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) and is meant to accelerate research directions that could reshape how scientists understand resistance, rather than simply adding incremental findings. Because it uses the NIH R21 mechanism, it is oriented toward high-impact, innovative projects that may involve novel hypotheses, new conceptual models, preliminary or emerging technologies, or proof-of-concept work that can lead to larger future studies.

A major emphasis of the FOA is the mechanistic study of microbial communities (often referred to as microbiomes) and the ways antibiotics disturb or reshape them. The program encourages research that digs into what microbial communities look like in different settings, how community structure and function change under antibiotic pressure, and which community interactions might promote or suppress the emergence of resistant organisms. It also highlights the idea that microbial communities might be harnessed to prevent disease, which can include studying protective community configurations, identifying community-derived signals that block pathogen colonization, or exploring ways to preserve or restore beneficial microbes following antibiotic exposure. In practical terms, the program is pointing applicants toward work that explains the "why" and "how" behind resistance development in real biological contexts, including community dynamics, ecological selection pressures, and microbial interactions that cannot be understood by studying single organisms in isolation.

In addition to microbiome and community-focused research, the FOA calls out interest in combination therapies as a strategy to address the emergence of resistance. This can involve investigating why certain drug combinations slow resistance development, identifying synergistic or antagonistic mechanisms, understanding how combinations affect within-host evolution, or defining principles for designing regimens that reduce the probability that resistant subpopulations will emerge. The key thread is mechanistic understanding: projects are expected to illuminate the biological processes and evolutionary pathways that enable resistance, and to generate insights that can inform better intervention strategies down the line.

This opportunity is explicitly labeled "Clinical Trial Not Allowed," meaning applications should not propose clinical trials as defined by NIH (for example, prospective studies in humans that assign participants to interventions to evaluate effects on health-related outcomes). The focus is therefore on basic, translational, preclinical, computational, or experimental research that advances understanding of resistance mechanisms without conducting a clinical trial. Depending on NIH’s specific definitions and institute policies, applicants typically aim for laboratory studies, animal model work, in vitro systems, systems biology, genomic and metagenomic approaches, and other mechanistic frameworks that do not meet the NIH clinical trial definition.

The award ceiling listed for the opportunity is $200,000, reflecting the smaller, exploratory nature of the R21 mechanism. While the posting does not specify the exact number of expected awards, the intent is to seed a portfolio of innovative projects that can open up new lines of inquiry or generate compelling preliminary results for subsequent, larger-scale funding. The opportunity was created on March 28, 2018, and the original closing date shown is May 7, 2021, which is important for applicants to verify against any current NIH re-issues, active receipt dates, or updated funding announcements if they are looking to apply now.

Eligibility is broad and includes a wide range of domestic and non-domestic organizations. Eligible applicants include state, county, city, and 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; Native American tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofit organizations with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly notes additional eligible applicant types such as 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, U.S. territories or possessions, and foreign organizations (non-U.S. entities). This breadth reflects an intent to encourage participation from diverse institutional settings and to support research capacity across different communities and regions.

Overall, the grant opportunity is aimed at generating new mechanistic insights into antibiotic resistance by focusing on microbial community biology, antibiotic impacts on those communities, strategies to leverage microbiomes for disease prevention, and scientifically grounded exploration of combination therapies that may curb resistance development. The program is positioned as a research catalyst: it supports innovative, concept-advancing work that can clarify underlying mechanisms and lay the groundwork for future interventions, tools, and larger-scale studies to address antibiotic-resistant bacteria as a major public health threat.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Generating New Insights and Mechanistic Understanding of Antibiotic Resistance Development (R21 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 2018-03-28.
• Applicants must submit their applications by 2021-05-07. (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 $200,000.00 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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