Mitochondria are referred to as the powerhouse or batteries of the cell, this is because they
produce energy for the cell. To generate this energy (ATP) mitochondria build their own machinery,
using mitochondrial DNA (mtDNA) as a blueprint. Errors in the mtDNA are rare, but do occur, which
can lead to severe and progressive diseases often with fatal outcome. There is currently no cure for
mitochondrial diseases, and since the mtDNA is well defended by 2 layers of membranes, gene
therapy is not as accessible as for other genetic diseases. In this project we will explore 2 different
routes towards a treatment for mitochondrial diseases.
In the first route, we will design chaperone molecules able to stabilise critical but defective nucleic
acid components of the mitochondrial machinery involved in translating the blueprints for normal
protein synthesis in the mitochondrion (the cause of the more common mitochondrial diseases),
thus restoring ATP production.
In the second route, we will attempt to remove the faulty DNA from the mitochondria in a specific
way, leaving only healthy DNA. To do this, we will design a special molecule to target the mutant
mtDNA, and inhibit its replication, while any remaining healthy mtDNA can replicate undisturbed.
The discoveries made in this project will serve as a platform, from which we can further develop
possible therapies for mitochondrial diseases.