Advanced imaging and mathematical modelling of ageing and neurodegeneration in the nervous system

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This project is highly interdisciplinary at the cross-roads of mathematical modelling and cell-/neurobiological research involving advanced live imaging, electron microscopy (EM), tomography and genetics. It will investigate processes of ageing and degeneration in the nervous system, focussing on mechanisms underpinning the longevity of axons. Axons are the cable-like (~1mm in diameter, metres-long) extensions of neurons which wire the nervous system. These delicate structures are maintained for many decades in humans. They are key lesion sites in spinal cord injury, trauma and many neurodegenerative diseases (e.g. spastic paraplegia), and we lose 50% of our axons during healthy ageing. The essential structural backbone of axons is formed by continuous bundles of filamentous protein-polymers called microtubules. Disorganisation of these microtubule bundles leads to axon swellings correlating with axon decay, but the underlying mechanisms preventing/causing disorganisation are not at all understood. To gain this understanding, work on this project will use genetically induced MT disorganisation in combination with advanced imaging to capture volume and space relationships (EM) as well as the dynamics of MT disorganisation processes (live imaging). Based on the collected data and existing algorithms for MTs, computational/mathematical models describing MT disorganisation will be developed and the underlying rules deduced.Literature:axons: Prokop, 2013, Neur Dev 8, 17ff.genetics: Prokop, 2013, J Cell Sci. 126, 2331ff.mathematics: Ziebert, 2015, Phys Rev Lett 114, 148101ff.live imaging: Alves-Silva, 2012, J Neurosci 32, 9143ff.EM: Starborg, 2013, Nat Protoc 8, 1433ff.