Understanding tubulin regulation during neuronal development, ageing and degeneration

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Axons are slender, up-to-a-meter long, cable-like extensions of neurons which form the nerves and nerve tracts that wire our bodies and brain. These delicate cellular structures have to be maintained for an organism's life time and are often the first to be affected in ageing, injury and neurodegeneration. To understand such conditions and identify ways to improve axon maintenance and regeneration, we study the regulation of microtubules (MTs) which form parallel bundles running all along axons to form their structural backbones and life-sustaining transport highways. On this project, you will study MT polymerisation which is the key driver of MT bundle formation and of continuous MT turn-over that protects axonal bundles from senescence during ageing. You will focus on the problem of how tubulins (i.e. the building blocks of MTs) are made available and continuously supplied in the narrow axons, up to a meter away from the cell body. This fascinating topic is most relevant to axon biology and pathology but surprisingly little understood. Your pioneering work will be based on our recently published mechanistic model of axonal tubulin supply and MT polymerisation, deduced from our own data and general knowledge in the field [Ref.1]. You will use cutting edge methodologies to study (1) contributions made by axonal transport and local tubulin translation, (2) roles of the chaperone machinery of tubulin assembly, and (3) mechanisms of tubulin storage and gene expression regulation. For your studies, you will use neurons of the fruit fly Drosophila, which provides uniquely powerful genetic and cell biological means in order to efficiently generate new understanding that can then be applied to higher animals [Ref.2]. You will be able to capitalise on expertises of the host group (AP) on MT regulation and the Drosophila neuron model, of the first co-supervisor's group (TW) on high resolution imaging and quantitative approaches [Ref.3,4], and of the second co-supervisor's group (MA) on RNA visualisation and processing [Ref.5]. Your transferable, experimental skill training opportunities will include genetics, cell biology, molecular biology, imaging techniques (live, high resolution, axonal transport, spatial detection of RNA and translational activity), quantitative analyses and modelling, as well as expertise in the important research areas of cytoskeleton and neurobiology. Finally, AP is an expert in science communication [Ref.6] providing further training opportunities important for your future career.