Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN)

Molecular Mechanisms of Axonal Injury

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

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

Previous work (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 and characterized by an intermediate stage with focal axonal swellings that can persist for several days, progress to degeneration but also spontaneously recover. However, many questions about focal axonal degeneration remain open, e.g. what determines if an axon will recover or not, what happens at the earliest sights of injury, what mediates changes in the axonal shape.

Methods: fluorescence microscopy and minimal tags for protein labelling

We study mechanisms of axonal injury in mouse and in vitro models. In addition to more standard microscopy techniques (live cell and intravital widefield imaging, confocal microscopy), we use modern super-resolution microscopy techniques, such as stochastic optical reconstruction microscopy (STORM), to obtain molecular-scale information. We are also using and developing new cutting-edge protein engineering tools based on selective incorporation of unnatural amino acids (Nikić et al., Angewandte 2014; Nikić, Kang, Girona et al., Nature Protocols 2015; Nikić & Lemke, Current Opinion in Chemical Biology 2016; Nikić et al., Angewandte 2016). Unnatural amino acids give us a unique opportunity to introduce new properties/functional groups, such as dyes, affinity tags for proteomics, post-translation modifications, cross-linkers, optogenetic tools, etc. into proteins at a single cell and even whole organism level.

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.Nikic[at]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