Our cells are constantly exposed to damaging stress from both external sources, such as UV rays, as well as internal sources, including free radicals produced by faulty mitochondria. Thankfully we have multiple ways to deal with this. One such protection mechanism is autophagy, an intracellular membrane-driven lysosomal degradation pathway. Autophagy protects cells by eliminating impaired and/or toxic components, which could lead to damage if left to persist. Because of this role, disruption of autophagy can have dire consequences and has been linked to many diseases including cancer, neurodegeneration and heart disease.

The goal of our research is to find ways to regulate this as yet poorly defined pathway so that autophagy can be used as a tool to treat disease. To do this, we need to identify physiological autophagy-inducing signalling pathways and determine how these signals trigger autophagosome formation. Towards this endeavor, we are focused on the ULK1 protein kinase, as this is critical for autophagy induction, yet how it does this is unclear.

Recently we developed novel ways to detect mitophagy, the autophagy of mitochondria, disruption of which is implicated in Parkinson’s disease. We have uncovered multiple instances of physiological mitophagy, for example in dopaminergic neurons within the midbrain, and our objectives are to resolve these mechanisms, delineate the relevant signalling pathways and determine how they relate to development and disease.