Ideas Lab: Use-Inspired Acceleration of Protein Design | 24 550

Opportunity Information: Apply for 24 550

The National Science Foundation (NSF), through its Directorate for Technology, Innovation and Partnerships (TIP), is funding an Ideas Lab called "Use-Inspired Acceleration of Protein Design" (USPRD). The core goal is to push protein design from impressive computational capability into faster, more reliable real-world deployment, especially in areas that matter for U.S. economic competitiveness and the broader bioeconomy. The opportunity builds on recent leaps in predicting protein 3D structure from sequence and designing proteins with targeted behaviors, advances fueled by large public datasets (such as the Protein Data Bank), modern AI and machine learning methods, and high-throughput experimental characterization. A major motivation is that better in-silico accuracy reduces how many expensive, time-consuming wet-lab iterations are needed, speeding translation from concept to validated protein function.

USPRD is explicitly focused on use-inspired and translational outcomes rather than purely exploratory research. It emphasizes two big technical and application pushes. First, it seeks to accelerate protein design for applications beyond human therapeutics, calling out areas like advanced materials, biomanufacturing, agriculture and food security, environmental remediation, sustainability, and climate-related challenges. Second, it aims to expand the reach and fidelity of prediction and design models so they can handle enzymes and even families of enzymes, which is harder than designing static structures because enzyme function depends heavily on dynamics, conformational changes, and mechanistic features that are not fully captured by many current modeling approaches. In practice, this means NSF is looking for breakthroughs that make enzyme design more accurate, more generalizable across enzyme families, and more grounded in realistic molecular motion and function.

The solicitation frames the desired breakthroughs as a coordinated package rather than isolated projects. It calls for (a) use-driven protein design efforts that produce novel proteins with specific, testable characteristics and demonstrate their real-world application, with an example being enzymes or enzyme families designed and characterized to degrade particular bio-contaminants to support sustainability goals. Alongside those demonstrations, NSF wants (b) shared infrastructure such as software tools, datasets, and characterization services that protein designers can readily access and reuse. It also highlights (c) designer-facing components, meaning practical layers that make the infrastructure usable by the broader community and that enable collaboration with external protein designers running the use-driven activities. In addition, it seeks (d) ecosystem components like standards and roadmaps to align multiple stakeholders in an emerging protein design ecosystem; these may include open-source software and data repositories that help coordinate methods, benchmarks, and interoperability. Finally, it includes (e) workforce development to train translational talent, meaning people who can bridge computation, experimentation, product-focused development, and deployment needs in use-driven protein design.

A defining feature of this opportunity is that it will be run as an NSF Ideas Lab. Instead of the typical proposal-only process, the Ideas Lab model starts with an intensive workshop that brings together participants with diverse expertise and perspectives. The workshop is intended to shape and converge on an aggressive but feasible set of use-driven targets, while also identifying the infrastructure, designer-facing tools, ecosystem coordination pieces, and workforce elements needed to achieve those targets. In other words, the program is structured to catalyze teams and directions that can move quickly from concept to demonstration, with shared resources and community alignment built in from the start.

USPRD is organized into two technical tracks. Track I focuses on use-driven applications for small binders, which generally refers to designed proteins that bind specific targets with high affinity and specificity and can be used in areas like sensing, capture, diagnostics-like platforms outside traditional therapeutics, and process control in manufacturing or environmental settings. Track II focuses on the design and use of enzymes and families of enzymes, targeting the harder challenge of designing functional catalysts and extending design capabilities across related enzymes, which is central to biomanufacturing, green chemistry, pollutant breakdown, and other sustainability-driven applications.

Eligibility is broad across academia, industry, and other research performers. Proposals may be submitted by U.S. institutions of higher education (including two- and four-year colleges), U.S.-based for-profit organizations (including small businesses) with strong R&D or education capabilities and an innovation focus, and U.S.-based non-profit non-academic organizations such as independent research labs, observatories, museums, and professional societies tied to research or education. Tribal Nations that are federally recognized are also eligible. Foreign organizations may participate, but for collaborative projects involving U.S. and foreign partners, NSF support is limited to the U.S. portion of the work. Other Federal Agencies and Federally Funded Research and Development Centers (FFRDCs) may be eligible but are advised to consult the program before submitting. There are no restrictions on who may serve as PI, which can make it easier to assemble leadership structures that fit the interdisciplinary and translational nature of the work. For proposals involving an international branch campus of a U.S. institution (including via subawards or consultants), the submission must clearly justify why that overseas performance is beneficial and why the activities cannot be performed on the U.S. campus.

Key program details from the posting include an NSF opportunity number of 24-550, a grant funding instrument, an expected 8 awards, and an award ceiling of $3,750,000. The original closing date listed is 2024-08-30. Overall, the opportunity is designed to quickly translate state-of-the-art protein modeling and design into demonstrated, non-therapeutic applications and next-generation enzyme design capabilities, while simultaneously building shared tools, standards, access pathways, and a trained workforce that can sustain growth of a U.S.-centered protein design innovation ecosystem.

• The National Science Foundation in the science and technology and other research and development sector is offering a public funding opportunity titled "Ideas Lab: Use-Inspired Acceleration of Protein Design" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 47.084.
• This funding opportunity was created on 2024-02-22.
• Applicants must submit their applications by 2024-08-30. (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 $3,750,000.00 in funding.
• The number of recipients for this funding is limited to 8 candidate(s).
• Eligible applicants include: Others.

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