Understanding the Rules of Life: Microbiome Interactions and Mechanisms | 21 534

Opportunity Information: Apply for 21 534

The National Science Foundation (NSF) grant opportunity titled "Understanding the Rules of Life: Microbiome Interactions and Mechanisms" (URoL:MIM) is a cross-NSF research program built around one of NSF's long-term "Big Ideas" called Understanding the Rules of Life: Predicting Phenotype. The central aim is to move beyond simply describing microbiomes and instead uncover the underlying, cause-and-effect rules that explain how microbiomes are built, how they function, and how they change over time. NSF is looking for projects that can translate the massive amount of existing microbiome data into general, predictive frameworks that help explain emergent biological behavior such as stability, resilience, and adaptability across organisms, populations, and communities. Although proposals are submitted through NSF's Division of Emerging Frontiers in the Biological Sciences Directorate (BIO/EF), they are intended to be handled by a cross-disciplinary team of program directors because the science is meant to cut across traditional fields.

A key feature of the program is its broad definition of a microbiome: a community of different microbes living in a particular habitat, which can include both host-associated microbiomes (such as those connected to humans, animals, or plants) and non-host-associated microbiomes (such as soils, aquatic systems, built environments, or other natural settings). NSF emphasizes a three-way relationship among the microbiome, the host (when present), and the environment. In host-associated settings, the microbiome can shape host physiology, behavior, development, and overall fitness; the host can influence microbial metabolism, community dynamics, and microbial evolution; and the surrounding environment (biological, chemical, physical, and even social factors) both affects and is affected by the host-microbiome system. The solicitation is essentially asking researchers to treat microbiomes as dynamic systems with feedback loops, rather than static lists of organisms.

NSF invites integrated, interdisciplinary proposals that generate new knowledge in multiple disciplines and that build causal explanations, not just correlations. Competitive projects are expected to propose clearly framed hypotheses about relationships within microbial communities and across the microbiome-host-environment triangle, and then test those hypotheses using strong experimental and/or computational designs. The program encourages development of new tools and approaches, including computational and mathematical methods (for example, new modeling strategies, inference methods, or scalable analytics) as well as experimental platforms (for example, improved manipulative experiments, synthetic or model microbiomes, or new measurement technologies). Example thrusts specifically highlighted include: explaining microbiome function and interactions in natural or model systems; identifying the chemical and molecular mechanisms that enable communication between hosts and microbes or among microbes; and performing comparative analyses across microbiomes to detect emergent properties that reveal broader principles of living systems.

Another major theme is generalizability across scales. NSF wants funded work to contribute to a broader research portfolio aimed at discovering "rules" that apply across different spatial scales and levels of biological complexity, from molecular and cellular processes up through organisms, populations, and communities. Time scale is also emphasized, with interest spanning everything from rapid interactions occurring in fractions of a second to long-term dynamics extending across evolutionary or even geologic time. The program is therefore not limited to any single organism, environment, or microbiome type; it is framed to support foundational science that can yield transferable principles and predictive understanding.

Because this is a convergence-style program, proposals must be genuinely novel and innovative in more than one discipline. NSF explicitly signals that projects should span fields such as biology, chemistry, computer science, engineering, geology, mathematics, physics, and the social and behavioral sciences, among others, as long as the integration is meaningful and advances causal understanding of microbiome mechanisms. The solicitation also stresses research rigor and reproducibility expectations: teams must use best practices in protocol documentation, sample selection, data collection, and analysis, and they must plan for data sharing and accessibility so results can be reused and built upon by others.

Beyond the research itself, URoL:MIM includes strong expectations around training and broader impacts. Projects must incorporate workforce development and/or innovative undergraduate and graduate education opportunities that expand the pipeline of researchers capable of doing microbiome interactions and mechanisms work. In practical terms, this means proposals should include concrete plans for training students and early-career scientists in cross-disciplinary microbiome science, potentially including team-based training models that combine wet-lab, computational, and quantitative skill building. NSF also indicates that projects should create societal benefit through public engagement and/or strengthening K-12 STEM education, aligning with NSF's broader expectation that federally funded research should contribute to education and public understanding as well as to scientific discovery.

In terms of funding and scale, URoL:MIM supports basic science projects of varying scope, with awards allowing a total budget of up to $3,000,000 and durations of up to five years. The opportunity is a discretionary NSF grant program (Funding Opportunity Number 21-534) with CFDA listings across multiple NSF program areas, reflecting its multi-directorate nature. NSF anticipated a small number of awards (the posting lists 8 expected awards), which reinforces that proposals are likely to be competitive and that the program is aiming for high-impact, integrative projects that can push the field toward mechanism-based, predictive microbiome science rather than incremental or purely descriptive studies.

• The National Science Foundation in the science and technology and other research and development sector is offering a public funding opportunity titled "Understanding the Rules of Life: Microbiome Interactions and Mechanisms" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 47.041, 47.049, 47.050, 47.070, 47.074, 47.075, 47.076, 47.079, 47.083.
• This funding opportunity was created on Nov 25, 2020.
• Applicants must submit their applications by Feb 23, 2021. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• The number of recipients for this funding is limited to 8 candidate(s).
• Eligible applicants include: Others (see text field entitled Additional Information on Eligibility for clarification).

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