Systems Biology Approaches using Non-Mammalian Laboratory Animals to Uncover Causes of Neurodegeneration that Might Underlie Alzheimers Disease and Related Dementias (R01 Clinical Trial Not Allowed) | RFA AG 18 021

Opportunity Information: Apply for RFA AG 18 021

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), released this funding opportunity announcement (FOA) to support basic research that uses systems biology in non-mammalian laboratory animals to uncover biological causes and mechanisms of neurodegeneration that could be relevant to Alzheimers disease (AD) and related dementias (ADRD). The central emphasis is on discovery science: applicants are expected to generate and analyze large-scale, network-oriented data to reveal molecular interactions and regulatory relationships that may drive neurodegenerative processes, make them worse, or protect the nervous system from them. Rather than focusing on single genes or single pathways, the FOA is aimed at identifying broader molecular networks and systems-level behavior that can explain how neurodegeneration emerges and progresses, especially in ways that may connect to aging and cognitive decline.

A defining feature of the opportunity is the required use of systems biology approaches, particularly the construction and interrogation of interaction networks and regulatory networks. In practical terms, this points toward work that integrates multi-omic or high-dimensional datasets (for example, transcriptomics, proteomics, metabolomics, epigenomics, or similar large-scale data types) with computational and statistical modeling to infer network structure and to identify key nodes, modules, and control points that influence neuronal survival, stress responses, proteostasis, synaptic function, inflammation-like processes, or other neurodegeneration-relevant biology. The expectation is that this network-focused strategy will produce insights that are difficult to obtain through traditional reductionist experiments, such as discovering emergent properties of gene regulation, pinpointing master regulators, mapping pathway crosstalk, or identifying protective network configurations that correlate with resilience.

The FOA specifically requires non-mammalian laboratory animal models, and it explicitly excludes studies that involve humans or experiments with mammals. That means the funded experimental work must be conducted in non-mammalian systems, which commonly include model organisms such as Drosophila (fruit fly), Caenorhabditis elegans (nematode worm), zebrafish, or other established non-mammalian laboratory species suited to genetics, high-throughput experimentation, and systems-level measurement. While the experimental organism must be non-mammalian, the FOA also recognizes that network building and interpretation may benefit from external datasets. As a result, data used to construct or refine networks can include information derived from humans or other mammals where AD, related dementias, or aging-associated cognitive decline have been observed, as long as the proposed studies themselves do not include human subjects research or mammalian experimentation. In other words, applicants can leverage existing mammalian or human datasets for comparative or integrative network analysis, but the experimental testing and primary model work supported by the award must remain non-mammalian.

Another notable point is that the FOA does not require applicants to use the currently popular genetically modified animal models traditionally used in AD research. Because the announcement is oriented toward discovery, investigators are free to use existing AD-related transgenic constructs in non-mammalian species if appropriate, but they are not obligated to rely on canonical AD model paradigms. This creates room for proposals that explore fundamental neurodegenerative biology through unbiased screens, natural variation, perturbation libraries, environmental or metabolic stressors, aging paradigms, or novel genetic manipulations that may reveal upstream drivers and network vulnerabilities that later translate to mammalian or human disease contexts. The underlying idea is that well-chosen non-mammalian systems, combined with rigorous network inference and systems analysis, can illuminate conserved biological mechanisms that might underlie neurodegeneration and ultimately inform AD/ADRD research directions.

From an administrative and eligibility perspective, the award mechanism is an NIH R01 research project grant, and clinical trials are not allowed under this announcement (R01 Clinical Trial Not Allowed). The FOA is categorized as discretionary funding and falls under the NIH health research activity area (CFDA 93.866). A wide range of organizations are eligible to apply, including state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments and other tribal organizations; public housing authorities; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (including small businesses); and other entities. The FOA also explicitly notes eligibility for a variety of institution types and organizations such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISI), as well as faith-based or community-based organizations, non-U.S. (foreign) entities, regional organizations, and U.S. territories or possessions. The opportunity was created on 2017-11-06 with an original closing date of 2018-02-21, and it is identified as RFA-AG-18-021.

Overall, this FOA is designed for teams that can combine non-mammalian experimental strengths (genetics, speed, throughput, well-characterized biology) with modern systems biology (network construction, integrative analytics, modeling, and validation) to discover molecular network logic relevant to neurodegeneration. The intended outcome is a clearer, more connected map of the biological processes that cause or modify neurodegenerative change, including candidate network hubs or regulatory programs that could later be explored as therapeutic targets, biomarkers, or mechanistic explanations for vulnerability and resilience in AD and related dementias.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Systems Biology Approaches using Non-Mammalian Laboratory Animals to Uncover Causes of Neurodegeneration that Might Underlie Alzheimers Disease and Related Dementias (R01 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): 93.866.
• This funding opportunity was created on 2017-11-06.
• Applicants must submit their applications by 2018-02-21. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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.

Apply for RFA AG 18 021

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