Midway Evaluation - Novin Balafkan

Using pluripotent stem cells (iPSC) to model mitochondrial disease and study tissue specific manifestations caused by POLG mutations

Novin Balafkan

Co-supervisor: Charalampos Tzoulis, MD, PhD

Co-supervisor: Janniche Torsvik, PhD

 Abstract:

The main aim of the project is to make a reliable model using induced pluripotent stem cells (iPSCs) for one of the commonest mitochondrial disease in Norway known mitochondrial spinocerebellar ataxia and epilepsy (MSCAE). Two relatively common mutations in the polymerase gamma (POLG) gene, A467T and W748S have been shown to be the genetic cause of this receive disease.^1,2

Using postmortem tissues, Professor Laurence Bindoff and his group have shown POLG mutations can affect mitochondrial DNA (mtDNA) and the results appear both qualitative (point mutation or multiple deletions) or quantitative (depletion) in different tissues. High energy consumption tissues such as brain, liver and skeleton muscles are more vulnerable to these mutations, however heart tissue appear unaffected.³ Tissue specificity is one of the mysteries of mitochondrial disease and to solve this mystery, and find the answer to several unanswered questions such as molecular mechanism of this disease, and to develop possible treatments, we need a model.

We have chosen iPSCs as model as these cells carry the same genotype as the donor patient and the limitless self-renewal of these cells give us the chance to keep these cells for much longer compared to primary lines. Moreover, their potential to generate all three embryonic layers will give use the chance to differentiate themto specific cell types in large quantity for further analysis and drug screening.⁴

The final goal of this project is to generate and characterize all the three tissue lineages including neuronal, hepatic and cardiac lineages from the control and patient fibroblasts and make a reliable resource for further investigations.

Venue: Laboratory Building (Labbyget) 5,1/5,2