Understanding the role of mitochondrial transport in axonal regeneration
Funded in: 2013, 2014, 2015
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Problem: Regenerating axons require high energy
Target: Mitochondrial transport (mitochondria = cellular organelles which supply cellular energy)
Goal: Understanding the role of the mitochondrial transport during axonal regeneration and subsequently promote them both.
The cells in the central nervous system require high levels of energy. This energy is provided by cell organelles called mitochondria. Due to the extremely long distance between neuronal cell body in the brain and the targets of their axons in the spinal cord, high energy levels are required far from the neuronal cell bodies. Therefore the precise regulation of mitochondrial transport within the cell is crucial to maintain neuronal physiology. There is only little knowledge about its importance in axonal injury and regeneration.
Latest research demonstrated the proof of principle that neurons can regenerate their axons. In those regrowing axons, the energy supplied by correct mitochondrial distribution along the regenerating axons is likely a critical factor for axonal regrowth of functional axons. The aim of this proposal is to understand the role of mitochondrial transport in supporting the robust axonal regeneration.
The intracellular transport depends on structures of the cytoskeleton, the microtubules. Microtubules consist of protein filaments, and the mitochondria are moved along these axonal microtubules in anterograde and retrograde direction by transport proteins. The key regulators of this transport system are not known.
To decipher the role of mitochondrial transport during axonal regeneration this project will
- Study in- vitro the mitochondrial transport in regenerating neurons by live imaging. A state of the art imaging facility allows the analysis of the parameters of mitochondrial movement like motion, direction speed or distance traveled.
- Identify the proteins responsible for the increased mitochondrial transport during regeneration (by a proteomic screen or alternatively a mRNA screen)
- Characterize in-vivo the mitochondrial transport during regeneration
The goal is to shed light on the role of mitochondrial transport during axonal regeneration and decipher mechanism to promote mitochondrial transport to regenerate functional axons.