Age-related Macular Degeneration (AMD) impacts the macula region within the retina, responsible for providing humans with high visual acuity and color vision. AMD is a debilitating, progressive disease that leads to irreversible vision loss among older adults, and its precise causes remain elusive, impeding the development of effective treatments. While both oxidative stress and inflammatory pathways have been associated with AMD, the specific pathophysiology and molecular pathways driving AMD progression remain incompletely understood.

Dysregulation of Alternative Polyadenylation (APA) has been implicated in influencing gene expression related to photoreceptor function, angiogenesis, inflammation, and oxidative stress—critical factors in AMD pathogenesis. This project aims to shed light on the role of APA and its regulation by RNA-binding proteins (RBPs) in the retina, with a particular focus on responses to oxidative stress as observed in AMD. We integrate high-resolution spatial transcriptome data, molecular biology techniques, and computational data analysis to elucidate the function and mechanisms of key RBPs that regulate APA in AMD pathogenesis. We further develop novel deep learning models to uncover the RBP regulatory code governing APA in spatial-temporal regulation.

This project is funded by the Australian National Health and Medical Research Council (NHMRC) Ideas Grants Scheme.