Exploring Proteogenomic Approaches to Unravel the Mechanisms of Mis-Folded Protein Accumulation in Tauopathies

This NOFO invites innovative research proposals to explore the accumulation of misprocessed proteins in Tauopathies within specific brain regions and cell types. This NOFO encourages collaborative efforts to create advanced single-cell or single-cell type proteogenomic platforms. These platforms aim to shed light on dynamic changes in protein-misfolding responses in neuronal proteomes and their potential biological consequences during aging and the development of AD/ADRD.

Using the proteogenomic approach, this NOFO aims to accomplish the following:

• Create a comprehensive database of misprocessed and aberrant proteins in selected mouse models of human Tau diseases.
• Cross-validate the presence of misprocessed and aberrant proteins in human AD/ADRD brains.
• Identify new molecular pathways and novel misprocessed protein-protein interaction networks that are not currently in most datasets.
• Define novel mechanisms through which misprocessed and aberrant proteins influence the onset and progression of neurodegeneration in tauopathies.
• Identify disease specific therapeutic targets in neurodegenerative diseases.
• It is expected that applications responding to this initiative will use the latest cell-type-specific labeling and proteogenomic techniques with suitable model systems to understand the etiology of tauopathies in aging and AD.

Non-responsiveness Criteria

Applications that only provide a global view of gene expression without any subcellular, cell-type, and brain regional specificity will be considered non-responsive to this NOFO and will be withdrawn prior to review. Examples of non-responsive studies include, but are not limited to, the following:

• Studies that use model organisms expressing AD-related genes in peripheral and non-CNS tissues.
• Studies that solely propose to use single and cell-type-specific RNAseq, transcriptomic, proteomic and epigenetic analyses without any functional validation.
• Studies that propose to generate new animal models and methodologies without a clear connection to the proteome dynamics of brain aging and AD.

 A letter of intent is requested by May 10, 2024 and the application receipt date is October 28, 2021 (No continuous and late applications will be accepted for this Funding Opportunity Announcement)