Principal Investigator: Laurence Bindoff

In projects led by Prof. Bindoff, we have generated cell and mouse models of impaired mtDNA homeostasis. Impaired mtDNA homeostasis due to POLG mutations results in the same pattern of mitochondrial dysfunction as seen in the brain with aging and multiple CNS disorders including PD, dementia, ALS and MS. We have induced pluripotent stem cells (iPSC) derived neurons and astrocytes from patients with POLG mutations. By co-culturing these, we will construct a cell model of mtDNA damage in the CNS and use it to screen for compounds that reverse/slow the development of mtDNA abnormalities. Outcome measures will include mitochondrial membrane potential and the amount of TFAM (which reflects the amount of mtDNA/cell) in flow-based assays. In addition to iPSC, we have a mouse model with a neurological phenotype and impaired neuronal mtDNA maintenance due to POLG mutations.