Large Scale Production of Perturbagen Induced Cellular Signatures (U54) | Apply Online

Opportunity Summary:

The National Institutes of Health (NIH) funding opportunity titled "Large Scale Production of Perturbagen Induced Cellular Signatures (U54)" (Funding Opportunity Number RFA-RM-10-003) was created to launch a pilot-scale, high-throughput data production effort under the Library of Integrated Network-based Cellular Signatures (LINCS) program. The central idea is to generate and organize large, standardized datasets that capture how cells respond when they are intentionally perturbed by different agents, then use those response patterns to draw mechanism-based connections across genes, pathways, drugs, and disease-relevant biology. In practical terms, the program aims to turn many individual perturbation experiments into a coherent, searchable knowledge base of cellular "signatures" that the broader research community can use for years.

The scientific focus is on systematically collecting informative molecular activity and cellular feature readouts after applying a wide range of perturbing agents to carefully selected cell types. The FOA explicitly highlights perturbagens such as siRNAs (used to reduce or silence gene expression) and small bioactive molecules (including compounds that can mimic, inhibit, or otherwise modulate biological targets). By applying these perturbations in a controlled and scalable way across selected cell models, awardees would generate response signatures that can be compared across conditions to reveal functional relationships. The long-term payoff NIH is aiming for is the ability to connect seemingly unrelated perturbations through shared downstream effects, which can illuminate pathways and networks that govern cellular behavior.

A major motivation behind LINCS in this FOA is enabling mechanism-based inference at scale. If two different perturbations produce highly similar cellular signatures, that similarity can suggest shared mechanisms of action, convergent pathway impacts, or related functional networks. This kind of resource can be used to support several important downstream applications: linking disease states to specific molecular or cellular phenotypes; associating diseases with gene networks rather than single genes; and clarifying or predicting the mechanisms of action for known drugs (and potentially helping to reposition drugs by matching drug-induced signatures to disease-associated signatures). The program is framed as building a "long lived resource," meaning the datasets are intended to persist beyond the award period and be broadly reusable by the community.

This particular FOA is focused on pilot-scale production rather than a full mature production program. The expectation is that funded centers will deliver a usable initial resource while simultaneously tackling the practical challenges that determine whether LINCS can scale and remain reliable. The FOA calls out three core issues that pilot awardees are expected to address: optimization of methods (so assays and workflows are robust and reproducible), integration of data (so outputs from different platforms, perturbations, and cell contexts can be combined and compared), and scalability (so the approach can grow to much larger volumes of perturbations and signatures without breaking in quality, cost, or throughput). In other words, NIH is not just paying for data generation; it is paying for production-grade processes that can become a foundation for a much larger ecosystem.

The awards are structured as U54 Specialized Centers Cooperative Agreements. That mechanism matters because it signals substantial NIH program involvement and coordination, rather than a hands-off grant. Cooperative agreements are commonly used when NIH expects awardees to work closely with program staff and with other funded components, aligning on standards, timelines, deliverables, and data-sharing expectations. The FOA also makes clear that these pilot production efforts are meant to interact with additional LINCS components that were planned for future funding rounds, including efforts aimed at developing and integrating new production-ready technologies and building informatics and data analysis tools. The pilot centers funded here are essentially positioned as the early production backbone that will need to connect smoothly to later technology and analytics investments.

In terms of funding scale and timing, NIH anticipated making up to two awards in fiscal year (FY) 2010. Applicants could request up to three years of support. The FOA states that total program funds were expected to be about $2.7 million in FY 2010, ramping up to $5 million in each of FY 2011 and FY 2012, reflecting an intent to grow the effort over time as methods stabilize and throughput increases. The listing also provides an award ceiling of $900,000 (as recorded in the opportunity metadata) and an overall estimated total funding amount of $12.7 million across the program. There was no cost sharing or matching requirement.

Eligibility is broad and includes many kinds of U.S. organizations and governments as well as certain non-U.S. entities. Eligible applicants listed include public and private institutions of higher education, nonprofit organizations (including 501(c)(3) and non-501(c)(3) nonprofits), for-profit organizations (with small businesses explicitly included and other for-profits also eligible), and various levels of government such as state, county, city or township governments, special district governments, and independent school districts. The eligibility language also extends to Tribal governments and organizations, Alaska Native and Native Hawaiian Serving Institutions, Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), U.S. territories or possessions, regional organizations, and even non-domestic (foreign) entities, indicating NIH was open to assembling the strongest possible production capabilities and collaborations.

Administratively, the opportunity falls under NIH, is categorized as a discretionary program, and uses the cooperative agreement funding instrument under a health-related activity category (CFDA 93.310). The announcement was posted on February 26, 2010, with an original and current closing date of April 27, 2010, and it was archived on May 28, 2010. The NIH Office of Extramural Research (OER) webmaster contact was provided for access or linking issues, along with a link to the full announcement on the NIH grants site.

Overall, this FOA is best understood as NIH funding for a small number of coordinated, production-oriented centers to generate the first large wave of standardized cellular response signatures to genetic and chemical perturbations, while proving that the workflows, data standards, and integration approaches can scale. The deliverable is not just datasets in isolation, but an initial, community-useful resource designed to support network-level biology, drug mechanism discovery, and future computational analyses that connect perturbations, pathways, and disease states through shared cellular signatures.

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