Mitochondrial gene expression is a poorly understood but crucial process that is defective in many of our patients. 50-60% of all children with mitochondrial (mt) disease do not have a genetic diagnosis and 40% of these children have a generalised defect of mtDNA expression.
Correct expression of mtDNA is essential for life and genetic defects perturbing this process are an important cause of mitochondrial disease. Despite its crucial importance, a detailed understanding of mtDNA expression is still lacking. For example, there is no method for transfecting mammalian mitochondria in intact cells making it impossible to interrogate in vivo RNA/DNA elements implicated in gene expression, not one mitochondrial ribonuclease has been implicated in mtRNA degradation, there is no faithful in vitro reconstituted mitochondrial protein synthesis system and no high resolution structure is available of the mitoribosome.
It is our belief that to design effective therapies for patients with mitochondrial disease it is essential to increase our understanding of the molecular mechanisms and key factors that underpin human mtDNA expression.
The research theme aims to:
- Establish the genetic basis of mitochondrial disease in patients, enabling families to be counselled with definitive genetic advice
- Identify critical factors and pathogenic defects underlying mitochondrial gene expression
- Define the mechanisms regulating the quality control of mitochondrial protein synthesis