Research Awards
Skirmantas Kriaucionis
University of Edinburgh
Mentor: Adrian Bird
Investigation of Mitochondrial Defects in a mouse model of RTT
$100,000
Lay Progress Report (August 2005)
The MECP2 gene is often mutated in cases of the neurological disorder Rett Syndrome. The major suggested function of MeCP2 is to make some genes silent, that is to prevent them from producing proteins. It is likely that the cause of Rett Syndrome is the failure of mutated MeCP2 to repress its target genes. We initiated a screen for MeCP2 target genes and identified a group of genes in the brain of a mouse model of Rett Syndrome. Two of these genes which were mis-regulated belong to the mitochondrial respiration chain. Mitochondria are found within cells, and are responsible for the production of ATP, which is the main source of energy. The failure to efficiently produce energy might compromise energy-demanding cells such as neurons in the brain. While producing energy, mitochondria consume oxygen. We examined the mitochondrial function of by measuring oxygen consumption in the mouse model of Rett Syndrome and detected increased and inefficient respiration. Interestingly, abnormal oxygen consumption was detected when mice acquire Rett Syndrome symptoms. Additionally, we examined mitochondrial function by separating components of the respiratory chain and measuring their activities. Finally to get a better insight into the MeCP2 role in silencing genes, we created and tested a construct which allows the regulation of MeCP2 presence/absence using small molecules.
Skirmantas KriaucionisUniversity of Edinburgh
Mentor: Adrian Bird
Investigation of Mitochondrial Defects in a mouse model of RTT
$100,000
Lay Progress Report (August 2005)
The MECP2 gene is often mutated in cases of the neurological disorder Rett Syndrome. The major suggested function of MeCP2 is to make some genes silent, that is to prevent them from producing proteins. It is likely that the cause of Rett Syndrome is the failure of mutated MeCP2 to repress its target genes. We initiated a screen for MeCP2 target genes and identified a group of genes in the brain of a mouse model of Rett Syndrome. Two of these genes which were mis-regulated belong to the mitochondrial respiration chain. Mitochondria are found within cells, and are responsible for the production of ATP, which is the main source of energy. The failure to efficiently produce energy might compromise energy-demanding cells such as neurons in the brain. While producing energy, mitochondria consume oxygen. We examined the mitochondrial function of by measuring oxygen consumption in the mouse model of Rett Syndrome and detected increased and inefficient respiration. Interestingly, abnormal oxygen consumption was detected when mice acquire Rett Syndrome symptoms. Additionally, we examined mitochondrial function by separating components of the respiratory chain and measuring their activities. Finally to get a better insight into the MeCP2 role in silencing genes, we created and tested a construct which allows the regulation of MeCP2 presence/absence using small molecules.