How our nerves survive for decades
Axons are the up-to-meter long processes of nerve cells which form the biological cables that wire nervous systems. We lose 40% of axons towards high age, and neurodegeneration usually starts in axons. Most forms of axon degeneration correlate with defects of their life-sustaining long-range cargo transport from and to the very distant cell body (Prokop, 2021).
This transport is performed by motor proteins moving along MTs that form parallel bundles extending uninterruptedly through the entire axon (Prokop, 2020). Since this transport inflicts substantial mechanical load on MTs, they are at risk of losing their parallel arrangements and become disordered, thus triggering axonal transport defects and axonopathy (Prokop, 2021). A central question is therefore how these constantly challenged MT bundles can maintain their parallel architecture for decades.
To address this complex yet crucial question, we pioneered primary neurons of the fruit fly Drosophila as a uniquely powerful system (Hahn et al., 2019; Prokop, 2016; Prokop et al., 2013). These neurons are easy and fast to culture, show growth dynamics and MT bundle phenotypes reminiscent of mammalian neurons, the underlying mechanisms tend to be well-conserved hence biomedically relevant, and can be dissected with highly efficient genetic manipulations: up to ~5 mutations/transgenes can be combined in the same neurons, ideal to tackle problems of redundancy and to understand genetic networks rather than restrict to mechanisms of single factors. My group alone has generated an unprecedented pool of functional data for >50 actin- and microtubule-binding proteins, which has enabled us to uncover genetic networks and novel concepts of MT bundle regulation (Alves-Silva et al., 2012; Beaven et al., 2015; Hahn et al., 2021; Qu et al., 2019; Qu et al., 2017), culminating in the "dependency cycle of local axon homeostasis" as a model explaining axonopathies (Prokop, 2021). Please get in contact if you are interested in a possible project on this topic based on your own ideas, or ideas that have emerged through our work.