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The role and regulation of microtubules during axon growth and degeneration


   Faculty of Biology, Medicine and Health

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  Prof Andreas Prokop  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Axons are the enormously long cable-like processes of neurons that wire the nervous system. These delicate structures have to be maintained for a life time. We lose 40% of our axons towards old age and many more in neurodegenerative diseases. Key components of axons are bundles of microtubules (MTs) serving as their structural backbones and highways for life-sustaining transport. We study the role and regulation of these bundles to understand axon growth, maintenance and degeneration.

Capitalising on uniquely powerful genetic analyses of neurons of the fruit fly Drosophila in culture and in vivo, we have identified a number of key mechanisms that maintain axonal MT bundles in order. These involve MT polymerisation and guidance, their cortical elimination and their stabilisation, all essential to maintain parallel MT bundles. An important further class of regulators are MT severing proteins including spastin, katanin and fidgetin, which disassemble MTs and maintain them in a dynamic state. Of these, spastin is closely linked to spastic paraplegia, a motorneuron disease-like condition, and we find that also loss of katanin has detrimental effects on axons.

On this project you will study the important roles of MT-severing proteins and unravel how they contribute to axonal longevity and decay. For this, you will use genetic manipulations of Drosophila neurons in culture and in vivo, advanced microscopy and image analysis, electron microscopy, as well as basic molecular biology and biochemistry. Furthermore, Andreas Prokop is a science communication expert providing important further training possibilities relevant for your future career path.

Training/techniques to be provided:
Training opportunities will include classical genetics and its application in Drosophila, cell culture techniques, analyses of brain tissues in vivo, advanced microscopy including super-resolution and live imaging, advanced image analysis, electron microscopy, basic skills in molecular biology and biochemistry, as well as science communication

Entry Requirements:
Candidates are expected to hold a minimum upper second class honours degree (or equivalent) in a biology subject. Candidates with a convincing interest in the subject matter are encouraged to apply. Some laboratory experience will help your application, but this can be discussed.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Prokop, A. (2016). Fruit flies in biological research. Biological Sciences Review 28, 10-14 -- https://tinyurl.com/ybvpoqmw
• Prokop, A., Beaven, R., Qu, Y., Sánchez-Soriano, N. (2013). Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance. J. Cell Sci. 126, 2331-41 -- http://dx.doi.org/10.1242/jcs.126912
• Hahn, I., Voelzmann, A., Liew, Y.-T., Costa-Gomes, B., Prokop, A. (2019). The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology bioRxiv, 10.1101/577320 -- https://www.biorxiv.org/content/10.1101/577320v3
• Illingworth, S., Prokop, A. (2017). Science communication in the field of fundamental biomedical research (editorial). Sem Cell Dev Biol 70, 1-9 -- https://tinyurl.com/yaj8gzrp
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