Michael Coleman
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Molecular mechanisms of Wallerian degeneration

Mechanisms of cell death are now reasonably well understood, but axons are a highly specialised part of neuronal cells and little is known about how they die. Michael Coleman's group is studying the molecular mechanism of Wallerian degeneration, a form of programmed axonal death, which is triggered by diverse degenerative stimuli including nerve injury, genetic defects of myelination and protein turnover, and toxic or genetic blockade of axonal transport.

To understand mechanisms of axon degeneration we need a reliable experimental model, such as Wallerian degeneration, the degeneration of axons distal to an injury. First described in 1850 by Augustus Waller, and named after him, Wallerian degeneration is now opening up to molecular analysis. Thus, research in this area is revealing insights into the molecular mechanisms of axon degeneration. In parallel, new developments in axon imaging using transgenically expressed fluorescent proteins are improving our understanding of the cellular events during axon degeneration.

Our studies focus on the mutant slow Wallerian degeneration protein (WldS), which we identified, and which delays Wallerian degeneration by tenfold in mice, rats and flies. We aim to identify other proteins in this regulatory pathway using a combination of methods. Our projects use methods in cell culture, mouse genetics, biochemistry, immunocytochemistry, confocal imaging in live and fixed tissue, electron microscopy, and pharmacological manipulation of signalling pathways.