Research in the O'Sullivan Lab
1. The study of ER-shaping proteins
The most common cause of the neurodegenerative disorder hereditary spastic paraplegia (HSP) are mutations in proteins that localise to and shape the endoplasmic reticulum (ER). However, the mechanisms by which loss of these ER-shaping proteins gives rise to axonopathy in HSP is not known.
We investigate the function of ER-shaping proteins using both the fruit fly, Drosophila melanogaster, and human cell lines.
Research in the O'Sullivan lab investigates the molecular mechanisms underlying neurodegenerative disorders. In particular, we the mechanisms by long axons, connecting neuronal cell bodies to distal synapses, degenerate.
2. Understanding the role of mitochondria in axonopathy
Mitochondrial disruption is a common feature of axonopathies including HSP and dominant optic atrophy (DOA; a form of inherited blindness). We are using in vivo models of disease to investigate how mitochondrial disruption contributes to neurodegenerative disease and to search for pharmacological agents which can restore mitochondrial organisation within disease models.
3. Investigation of the role of tubular ER in lipid homeostasis
Several lines of evidence have identified lipid homeostasis disruption in cellular and animal models of HSP. Given that lipid storage organelles, lipid droplets (LDs), are synthesised at and bud off from the ER, we are investigating how HSP-causing mutations affect contribute to neurodegeneration via altered lipid homeostasis.
