Team:
Mario Milani, Eloise Mastrangelo, Francesco Bonì
Collaborators:
Daniele Dell’Orco (UNIVR)
GCAP1 (GUCA1A) is a Ca²⁺-sensitive regulator of retinal guanylyl cyclase 1 (RetGC1), controlling cGMP production in photoreceptors. Disease-causing missense mutations disrupt this regulation, leading to constitutive RetGC1 activation, cGMP accumulation, and progressive cone and cone-rod dystrophies.
This project aims to define the structural and functional mechanisms underlying GCAP1 dysfunction and to identify novel therapeutic strategies. We combine structural biology, biophysics, and computational approaches to characterize pathogenic variants and their impact on RetGC1 regulation, supported by cellular assays and in vivo retinal models. In parallel, we are exploring small molecules that modulate GCAP1 conformation and oligomeric state.
Funding:
Fondazione Telethon
