Project Grant 2450845

The National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) awarded a $150,000 Project Grant to the University of South Alabama (USA) on March 15, 2025. The grant, titled "Mitochondrial Artificial Targeting (MART) to Augment mtDNA Repair", aims to enhance the natural repair mechanisms of mitochondrial DNA by improving the targeting of key repair enzymes to mitochondria without disrupting their other cellular roles. The project focuses on re-engineering the mitochondrial localization signals of five DNA glycosylases that specifically excise oxidized DNA damage, in order to improve their targeting to mitochondria and evaluate the functional impact on oxidative damage repair capacity, mitochondrial DNA stability, and mitochondrial function. The research leverages a novel computational framework to optimize the mitochondrial targeting signals, which will be validated experimentally. This work addresses a critical gap in the understanding of mitochondrial base excision repair, a pathway essential for maintaining mitochondrial DNA integrity in the face of oxidative stress. The project is expected to be completed by February 28, 2029.