The Webb Lab’s work on MARS2 focuses on a rare neurodevelopmental disorder, COXPD25, caused by pathogenic mutations in MARS2. This gene is vital for mitochondrial protein synthesis and energy production. COXPD25 presents in infancy with developmental delays and hearing loss. In affected patients, Webb Lab researchers identified MARS2 mutations that impair mitochondrial function, specifically in respiratory chain complexes I and IV. By studying how MARS2 dysfunction disrupts mitochondrial activity, the lab aims to uncover common pathways underlying various neurodevelopmental disorders, potentially leading to novel treatment strategies.
Studying MARS2 in the Lab
To study the neurological effects of COXPD25 and create a model for other mtARS disorders, researchers are using two approaches:
1. A knock-in mouse model with a patient-like Mars2 mutation.
2. Human iPSC-derived neurons that model brain development in patients.