Axon degeneration and axon loss are unifying early events that are shared by many neurological diseases. Indeed, it has been estimated that the lifetime risk for a disease involving axon degeneration might be as high as 50%.
Our laboratory, which is a joint research group of Technical University of Munich and DZNE, tries to understand the cell biology underlying these central events in neurodegeneration. For this, we use a combination of in vivo imaging (including two-photon microscopy and correlated ultrastructure), genetic labeling and molecular interventions to visualize and modulate subcellular dynamics during axon degeneration (for a review, see: Misgeld & Kerschensteiner, Nature Rev Neurosci 2006). Our current focus is on axon loss in a range of settings, including developmental, traumatic and inflammatory models, in which we visualize the behavior of various cell types, such as neurons, glial and immune cells, and devise new assays to monitor central cell biological pathways – both in mouse and zebrafish models. One focus of the lab has been to visualize axonal transport, neuronal mitochondria and subcellular signaling events (for reviews, see: Misgeld & Schwarz, Neuron 2017; Plucinska & Misgeld, 2016). Importantly, many of these pathways are targets for ongoing therapy development in many laboratories. However, assaying the effects of such interventions in many cases has remained difficult – so our work provides much needed in vivo assays for neuronal cell biology, as well as insights into the mechanisms underlying degeneration.
Over the past years, our laboratory has focused on the following topics:
- Development of new imaging approaches to study axon degeneration in vivo in the mouse nervous system (Kerschensteiner et al., Nat Med 2005; Bishop et al., Nat Meth 2011)
- Design of tools and assays to study axonal transport and mitochondrial dynamics (Misgeld et al., Nat Meth 2007; Plucinska et al., J Neurosci 2012), cytoskeletal remodeling (Kleele et al., Nat Comm 2014), as well as subcellular signalling (Breckwoldt et al., Nat Med 2014).
- Disruptions of axonal transport, e.g. in models of motor neuron disease (Marinkovic et al., PNAS 2012)
- Mechanisms of axon degeneration in models of neuroinflammatory diseases, such as multiple sclerosis (Nikic et al., Nat Med 2011; Sorbara et al., Neuron 2014; Romanelli et al, Nat Comm 2016) and neuromyelitis optica (Herwerth et al., Annals Neurol, 2016)
- Axonal dynamics after spinal cord injury (Williams et al., Nat Com 2014) and during physiological axon remodeling (Brill et al., Neuron 2016).
Beyond this research program, our lab is also centrally involved in coordinating the DFG-funded Excellence Cluster ‘Munich Cluster of Systems Neurology’ (SyNergy), for which we are operating an electron microscopy hub that is focused on correlated light-electron microscopy using advanced fixation and volume reconstruction techniques.