Objetivo
The ultimate goal of this project is to identify the molecular mechanism underlying autosomal Dominant Optic Atrophy (DOA), a devastating genetic disorder leading to degeneration of retinal ganglion cells and childhood blindness.
The gene defective in DOA maps to chromosome 3q28-29 and is called Optic Atrophy type 1 (OPA1). OPA1 encodes a mitochondrial GTPase which carries several mutations in humans with DOA. OPA1 is a mitochondrial protein involved in membrane fusion events that are required for mitochondrial integrity and maintenance. Loss of OPA1 function leads to mitochondrial fission, loss of mitochondrial DNA, and respiratory deficits.
A decline in mitochondrial function is well recognized in neurodegenerative diseases and aging, and leads in the case of DOA to degeneration of optical neurons that result in blindness. The biochemical function of OPA1 is unknown. OPA1 is a 961 amino acid residue membrane protein that belongs to a family of highly conserved GTPases related to Dynamin.
Intriguingly, the majority of missense mutations found in DOA patients reside in the highly conserved GTPase domain. In order to unravel the molecular mechanism behind DOA and to set the groundwork for the development of DOA therapies, a detailed understanding of OPA1 function is necessary. To achieve this, we plan a functional characterization of OPA1 by means of biochemical and structural studies.
We have already established proof of concept with obtaining a purification protocol, preliminary functional characterization and initial crystallization conditions of OPA1. With funding of this proposal we will carry out a comprehensive functional characterization of OPA1 and shed light on its role in DOA.
Ámbito científico
Palabras clave
Convocatoria de propuestas
FP6-2004-MOBILITY-12
Consulte otros proyectos de esta convocatoria
Régimen de financiación
EIF - Marie Curie actions-Intra-European FellowshipsCoordinador
SALZBURG
Austria