Investigating Mitochondrial-Nuclear Communication in AD/ADRD (R01 Clinical Trial Not Allowed)

The National Institute on Aging (NIA) at the National Institutes of Health (NIH) has released a Notice of Funding Opportunity (NOFO) inviting applications for R01 research grants to study mitochondrial-nuclear communication in Alzheimer’s Disease (AD) and Alzheimer’s Disease-related dementias (AD/ADRD). The purpose of this NOFO is to expand understanding of how mitochondrial dysfunction affects nuclear gene expression and vice versa, a relationship that plays a critical role in cellular health and may contribute to AD/ADRD onset and progression. This research seeks to uncover mechanisms by which mitochondrial-derived metabolites impact nuclear processes and, reciprocally, how nuclear functions affect mitochondrial activity. The findings could be foundational for novel AD/ADRD therapies targeting mitochondrial function and could advance knowledge of aging and neurodegeneration more broadly. The NOFO calls for innovative research that leverages new tools and technologies to investigate mitochondrial-nuclear communication in the context of AD/ADRD. Research topics may include how mitochondrial dysfunction alters AD/ADRD risk gene expression, impacts epigenetic changes in nuclear DNA, or influences overall neuronal health. Proposals may also focus on the role of mitochondrial heteroplasmy (variability in mitochondrial DNA within cells), differences in cellular responses, and the functional consequences of mitochondrial-nuclear interactions on disease progression. This research is intended to support exploratory work in this emerging field of organelle communication and foster advancements in understanding AD/ADRD pathology. Eligible applicants include higher education institutions, nonprofit organizations, for-profit entities, local and state governments, as well as foreign and international organizations. The budget for each proposal should be aligned with the project’s actual needs, with no specific budget cap set, although total funding for this NOFO is anticipated to be $4 million in FY 2025 to support approximately eight awards. The project period can be up to five years. Only applications that do not propose clinical trials are eligible; the NOFO emphasizes studies of molecular and cellular mechanisms rather than interventions or treatments involving human participants. Application submissions must adhere strictly to NIH guidelines as outlined in the Research (R) Instructions of the NIH Application Guide. Submissions will be reviewed based on their scientific merit, with a focus on criteria including significance, investigator qualifications, innovation, approach, and the scientific environment. Additional review criteria cover human subjects protection, inclusion of women, minorities, and individuals across the lifespan, and considerations for vertebrate animals, if applicable. Proposals that are not aligned with the NOFO’s specific interest in mitochondrial-nuclear communication in AD/ADRD will be considered nonresponsive and withdrawn from review. Key dates include an optional Letter of Intent due by October 7, 2024, and the full application submission deadline on November 7, 2024. Reviews are expected in early 2025, with earliest project start dates anticipated by July 2025. Applicants must complete necessary registrations in the System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (for foreign applicants), eRA Commons, and Grants.gov well ahead of submission. This funding opportunity aligns with NIH’s commitment to advancing the field of neurodegeneration and addresses the rising public health challenge posed by AD. NIA encourages prospective applicants to contact the designated NIH representative for guidance on aligning research proposals with NOFO objectives and eligibility criteria.