Molecular Mechanisms of Axonal Injury

Axonal biology: mechanisms and new chemical biology-based tools for studying molecular and cellular dynamics

Maintaining the integrity of axonal function and structure is crucial for the normal function of the nervous system. Axons transmit electrical impulses and transport cargos between neuronal cell bodies and synapses. Due to their unique roles and molecular organisation, they can cover remarkable distances and are highly susceptible to injury. In neuroinflammatory diseases, such as multiple sclerosis (MS), axons are damaged by infiltrating immune cells.

A prior study (Nikić et al., Nature Medicine 2011) identified a novel form of neuroinflammatory axon loss—focal axonal degeneration (FAD). Focal axonal degeneration is a sequential process, induced by neuroinflammatory oxidative stress. It is characterized by an intermediate stage featuring focal axonal swellings that can persist for several days, progress to degeneration, or even spontaneously recover. However, many questions regarding focal axonal degeneration remain unanswered, such as what determines whether an axon will recover or not, what occurs at the earliest sights of injury, and what mediates changes in the axonal shape.

Methods: fluorescence microscopy and minimal tags for protein labelling

We investigate the mechanisms of axonal injury using both mouse and in vitro models. In addition to conventional microscopy techniques, we employ super-resolution microscopy methods, including stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED), to gain molecular-scale insights into basic and translational neurobiological processes. Another major focus of our group is the development of cutting-edge protein engineering tools, which rely on the selective incorporation of unnatural amino acids and bioorthogonal click chemistry (Nikić-Spiegel, ChemBioChem, 2020; Nikić et al., Angewandte Chemie 2014; Nikić et al., Nature Protocols 2015; Nikić et al., Angewandte Chemie 2016). Unnatural amino acids provide us with a unique opportunity to introduce new properties and functional groups, such as dyes, affinity tags for proteomics, post-translation modifications, cross-linkers, optogenetic probes, into proteins at the single-cell and even whole-organism level. Building on my previous work using this technology for protein labeling and advanced microscopy in conventional cell lines (Nikić & Lemke, Current Opinion in Chemical Biology 2016), our group stands at the forefront of applying this approach to protein engineering and microscopy in more complex biological systems, such as primary neurons (Arsić et al., Nature Communications 2022; Stajković et al., Journal of Cell Science 2023; Taylor et al., Wiley Analytical Science 2023).

Funding

Work in our laboratory is supported by the Emmy Noether Programme of the German Research Foundation.

Open positions

We are always happy to hear from prospective Master, PhD and Postdoc candidates. If interested, please send an email to Ivana.Nikicspam prevention@cin.uni-tuebingen.de describing your motivation and research experience. Please do not forget to send us your short CV and contact details of 2-3 referees.

Selected Publications

For full access to the publications, follow the link to the Google Scholar page

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