The National Institute on Aging (NIA) awarded a $820,674 Project Grant under the Aging Research program (CFDA 93.866) to the University of Southern California (USC) to investigate the role of DNA damage-induced transcription errors in the accumulation of amyloid and prion-like proteins associated with aging and Alzheimer's disease.
The key products and services to be delivered include:
Screening a database of 260,000 transcription errors in human stem cells, brain organoids, and neurons to identify candidates likely to create amyloid peptides
Using cellular, biochemical, and biophysical tools, including cryo-EM and fluorescent imaging, to test the amyloid behavior of these proteins
Determining if DNA damage, specifically O6-methyl guanine lesions, can induce error-prone transcription and the generation of mutant proteins in human neurons
Evaluating whether O6-methyl guanine-induced transcription errors are sufficient to induce protein aggregation in human neurons
Testing if O6-methyl guanine-induced errors can affect the pathology of Alzheimer's disease in a mouse model
As part of this award, USC will collaborate with Mississippi State University as a sub-grantee to further investigate the mechanisms by which DNA damage-induced transcription errors contribute to the accumulation of amyloid and prion-like proteins.