Bateman:Research

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Overview

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.

Insulin/TOR signalling in the nervous system

We are interested in how the insulin/TOR signal transduction pathways control cell fate in the Drosophila nervous system. This pathway is highly conserved and performs critical functions in both the developing and adult CNS. Aberrant activity of insulin/TOR signalling can lead to disease and so understanding how this pathway act in the CNS will provide insight into pathogenic states such as neurodegeneration and brain cancer.

Insulin/TOR signalling in neurogenesis

Insulin signalling is best known for its role in glucose homeostasis and diabetes. However, this pathway also has critical roles in controlling processes such as cell growth, autophagy and ageing. We have discovered a novel role for the insulin pathway in the temporal control of neurogenesis in Drosophila photoreceptor (PR) neurons (Bateman & McNeill, 2004).

Photoreceptor differentiation (red) is delayed in insulin receptor clones (marked by the absence of GFP expression

More recently we have shown that insulin signalling interacts with the EGFR pathway in controlling PR cell fate (McNeill et al., 2008). Our current aim is to identify novel genes that are regulated by insulin signalling to control PR neurogenesis.

Insulin/TOR and FGF signalling in glial proliferation

Around 50% of the human brain is comprised of glial cells. Work in mammals and Drosophila has shown that specific glial populations actively divide during post-embryonic development. We have recently shown that large numbers of glia are generated by glial proliferation in the Drosophila postembryonic brain (Avet-Rochex et al, 2012). This process is regulated by concerted action of the insulin/TOR and FGF pathways. We are now investigating how glial proliferation is controlled by identifying new genes that regulate this process.

Clonal populations of proliferating glial cells, marked by GFP expression, in the Drosophila larval brain

Mitochondrial DNA inheritance in the nervous system

Mitochondria play critical roles in the generation of cellular energy, apoptosis, cellular calcium buffering and the generation of reactive oxygen species. Mitochondria also have important functions in normal ageing. Given these critical roles in cellular function and physiology, it is not surprising that mitochondria also contribute to a large number of pathogenenic states ranging from cancer to neurodegenerative diseases such as Parkinson’s.

We are interested in how correct mitochondrial DNA (mtDNA) is maintained. Maintenance of correct mtDNA copy number is essential for mitochondrial respiratory function and defects in mtDNA maintenance can cause a group of disorders known as mitochondrial DNA depletion syndrome (MDS). We have recently shown that the mitochondrial inner membrane translocase Tim17 can prevent mitochondrial DNA loss in a cellular model of mitochondrial disease (Iacovino et al., 2009).

Tim17 (outlined in red) is a component of the TIM23 mitochondrial inner membrane translocase complex

We are currently interested in understanding the mechanism and determining the therapeutic potential of Tim17 in preventing mitochondrial DNA loss. In addition, we are studying how mitochondrial DNA is maintained in the Drosophila CNS.

Overexpression of Tim17A in human NT2 cells carrying the A3243G mutation prevents mitochondrial DNA loss