NIH R01 Deciphering the Impact of RNA Modifications on Brain Aging and AD/ADRD

Funding Opportunity Number: RFA-AG-25-022

Deadlines
Letter of Intent: October 1, 2024
Submission: November 1, 2024

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to catalyze innovative research to elucidate the molecular landscape and functional implications of RNA modifications in brain aging and Alzheimer’s disease (AD) and AD-related dementias (ADRD). AD-related dementias include Lewy body dementia (LBD), frontotemporal dementia (FTD), vascular cognitive impairment/dementia (VCI/D), and mixed dementias. This NOFO supports applications focused on uncovering novel mechanisms underlying RNA modification-mediated processes and their impact on brain aging and the pathogenesis and progression of AD/ADRD. The ultimate goal is to identify targets for biomarker discovery and drug development for AD/ADRD.

Program Scope and Research Objectives

The purpose of this NOFO is to catalyze innovative research to elucidate the molecular landscape and functional implications of RNA modifications in brain aging and AD/ADRD. AD-related dementias include Lewy body dementia (LBD), frontotemporal dementia (FTD), vascular cognitive impairment/dementia (VCI/D), and mixed dementias. This NOFO supports applications focused on uncovering novel mechanisms underlying RNA modification-mediated processes and their impact on brain aging and the pathogenesis and progress of AD/ADRD. The ultimate goal is to identify targets for biomarker discovery and drug development for AD/ADRD.

Specific research areas that are of great interest include, but are not limited to, the following: Identify functionally relevant RNA modification sites and genes linked to AD onset and severity across multiple brain regions and cell types. Dissect tissue- and cell-specific epitranscriptome-induced biological changes.

  • Investigate temporal and spatial dynamics of RNA modifications driving brain aging and AD/ADRD. Elucidate the role of these modifications in signaling pathways and pathophysiological processes.
  • Characterize RNA modifying machinery including writers, readers, and erasers, and identify the cellular and subcellular location and function of these proteins during brain aging and over the development of AD/ADRD.
  • Dissect the cellular and molecular mechanisms of RNA modifications associated with the onset, progression, and severity of AD/ADRD and in brain aging. Examine the relationships between RNA modifications and AD vulnerability. Identify potential therapeutic targets.
  • Elucidate the interplay between different RNA modifications and RNA modifying proteins, and their functional roles.
  • Identify RNA modification signatures that can serve as potential biomarkers for disease onset, progression, and severity.
  • Explore therapeutic interventions interfering with RNA modifications and RNA modifying protein-mediated molecular pathways and cellular processes.
  • Develop novel in vitro, in vivo, and in silico methodologies and tools for the detection, quantification, and examination of functional impact of RNA modifications in the brain and AD/ADRD.

For more information, please see the opportunity webpage.