Department of Life Sciences and Systems Biology

Project description

Il progetto ha l'obiettivo di studiare il ruolo del fattore trascrizionale NR2F1 (COUP-TFI) nella funzione mitocondriale in un modlelo murino della malattia genetica rara BBSOAS 

 

English
Bosch-Boonstra-Schaaf optic atrophy-intellectual syndrome (BBSOAS) is a rare human disease (ORPHA: 401777) caused by mutations in the NR2F1 gene which encodes for the COUP-TFI transcriptional regulator, known for its multiple functions in brain development and postnatal brain plasticity. BBSOAS is characterized by a wide array of clinical features, with a prevalence of developmental delay and intellectual disability (ID). Recent reports indicate BBSOAS patients with abnormalities in mitochondrial energy supply due to a defective mitochondrial respiratory chain. In addition, data in the literature and our preliminary findings suggest that alteration in COUP-TFI function could be directly involved in mitochondrial dysfunction, a condition observed in several developmental disorders leading to ID. Despite this evidence, a direct link between COUP-TFI, mitochondrial dysfunction, and BBSOAS syndrome is still lacking. This proposal aims to explore novel aspects of BBSOAS pathophysiology by focusing on the role of COUP-TFI on mitochondrial function/dynamic in newborn neurons of the postnatal hippocampal dentate gyrus. We propose to study the consequences of COUP-TFI loss-of-function on mitochondria dynamic/function in inducible conditional mouse models by labeling mitochondria through retroviral injections and combining advanced imaging techniques for in vivo analysis. Moreover, potential targets of COUP-TFI action among the genes controlling cell metabolism and mitochondrial function will be identified through genome-wide and in silico analysis and validated on mutant brain tissue.

The project is based on a wealth of strong preliminary data and on a solid scientific background ensuring its feasibility.

Notes

Responsabile Silvia De Marchis