Project Title:

The Role of ER Architecture in Axonal Presynaptic Physiology

Project Summary:

I am a member of Professor Cahir O’Kane’s research group in the Department of Genetics and my PhD project is centred on the physiological consequences of the architecture of axonal ER nanotubules in Drosophila. My experimental approach is to manipulate axonal ER organelle structure in Drosophila to gain insight into the physiological mechanisms at play within the axon. I will achieve this by using mutant Drosophila larvae that I constructed by genetic crossing. I am utilising various approaches to conduct my research: performing larval axon dissections and microscopy in the lab and using computational skills to develop automated pipelines for analysis and data interpretation. The mutations I am studying are directly linked to the crippling, untreatable human disease, hereditary spastic paraplegia, a length dependant axonopathy that impacts lower motor function resulting in weakness and stiffness in the legs. This link with a life-altering disease peaked my fascination with the project. The lab has already done a lot of great work characterising the morphological changes that occur in the axonal ER as a result of the mutations. In my research, I hope to take this a step further and elucidate the physiological ramifications of the mutations, for example in calcium handling. In the bigger picture, I hope these findings could help in the wider community effort to develop better therapies for hereditary spastic paraplegia.