The overall focus of my laboratory is to understand basic processes in neural development by identifying the key pathways and genes involved and to use this information to provide novel insight into neuropathological disease. Our work will in the long term contribute to improving quality of life by providing new knowledge about nervous system development that can be used to develop strategies to regenerate neural cells and combat neuropathological disease.
Regulation of neurogenesis by mTOR signalling and its role in epilepsy
We are interested in how the mTOR signal transduction pathway controls neuronal differentiation and the role of this pathway in neurodevelopmental disorders. Hyperactivation of mTOR signalling causes the disease Tuberous Sclerosis Complex (TSC). TSC patients frequently suffer from neurodevelopmental disorders such as epilepsy and autism.
mTOR signalling in neurogenesis
mTOR signalling has critical roles in controlling processes such as cell growth, autophagy and ageing. We discovered a novel role for the mTOR pathway in the temporal control of neuronal differentiation in Drosophila photoreceptor neurons (see Bateman & McNeill, 2004).
More recently we have identified a novel complex of two proteins, Unkempt and Headcase, that act downstream of mTOR to regulate photoreceptor differentiation in Drosophila (see Avet-Rochex et al., 2014). We are currently study the role of the Unkempt and Headcase in the CNS in Drosophila and mammalian models systems. Understanding the function of these proteins and how they are regulated by mTOR will provide novel insight into how mTOR signalling contributes to neurological disorders like epilepsy and autism.
Mitochondrial dysfunction in the nervous system and its role in neurodegenerative disease
Mitochondria are cellular organelles that play vital roles in the generation of cellular energy, apoptosis, cellular calcium buffering and the generation of reactive oxygen species. Mitochondrial dysfunction is increasingly considered to be a critical factor in the development of neurodegenerative disease.
We are interested in how neurons respond to mitochondrial dysfunction and how this process can be modified as a treatment for neurodegenerative disease. We have previously used a genetic screen in yeast to identify genes that can prevent mitochondrial DNA loss in yeast and a cellular model of mitochondrial disease (see Iacovino et al., 2009).
Modelling mitochondrial dysfunction in Drosophila
We are currently developing a Drosophila model of neuronal mitochondrial dysfunction and using this to understand how neurons respond to mitochondrial dysfunction in vivo.
Mitochondrial neuropathology in dementia
We also use human neurodegenerative disease tissue to study the changes that result from mitochondrial dysfunction in diseases like Parkinson's (see Gatt et al., 2013).