PhD Top-up Scholarships
28/02/2016 → 28/02/2019
Prof Mike Ryan & Dr Michael Lazarou
Functionalisation of mitochondrial Complex I accessory subunits in health and disease
Mitochondrial complex I is the largest of the five enzymes which combine to perform oxidative phosphorylation, the primary source of energy within humans. Through this process, some of the macromolecules you eat as food are able to be broken down and converted into the energy that is essential for the healthy furrcti.oning of your body. Complex I can be considered as a huge molecular machine, comprised of 44 different protein subunits. When these subunits come together as they are supposed to, the machine can work and energy is generated. However, when some of the subunits are faulty, the machine does not assemble properly and the normal amount of energy is not generated. This lack of energy can manifest as various symptoms in mitochondrial disease, particularly in those organs that require the most energy, such as the eyes, heart, brain and skeletal muscle.
My research looks to investigate the individual role of these protein subunits, and how their mis-assembly may lead to mitochondrial disease. By using the gene editing tool CRISPR/Cas9, I aim to modify the genes of the constituent proteins in very specific ways, and determine how this change affects the assembly of complex I and changes to mitochondrial function. Clarifying the roles of each of these subunits is integral to determining how complex