PhD (BBSRC DTP): The evolution of nerves – understanding the roots of neurodegeneration

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How to apply: https://www.bmh.manchester.ac.uk/study/research/bbsrc-dtp/apply

• Application deadline: 21 January 2022
• Interviews: week commencing 7 March 2022

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Faculty of Biology, Medicine and Health, The University of Manchester

PhD Research Project Competition Funded Students Worldwide

Andreas Prokop  

Viki Allan

Matt Ronshaugen

Details

Axons are slender extensions of neurons which can be meter-long and form the biological cables that run through our nerves and brains to hardwire the nervous system. In humans, axons must survive for up to a century; we lose ~40% of axons towards high age and many more in neurodegeneration, but the causes are poorly understood.

To understand axon maintenance and pathologies, we are focussing on the bundles of microtubules (MTs) that run all along axons – be it in a tiny fly or in a human [Ref1]. These bundles determine axon structure and form the highways for life-sustaining axonal transport. Accordingly, MT bundle decay causes axon degeneration. But the mechanisms that maintain these bundles (and might fail in pathology!) are little understood [Refs2,3].

Here we will test the long-standing, but poorly proven hypothesis that axonal bundles are cross-linked by MT-binding proteins. For this, we will study potential architectural functions of MAP1B/Futsch proteins, known to be enriched in axons across the animal kingdom [1]. They show an intriguing evolutionary profile: N- and C-terminal regions are potentially MT-associating and evolutionary well conserved, whereas middle regions show enormous sequence and length differences [FigS1 in Ref1]. MAP1B/Futsch proteins may therefore act as flexible spacers, with their length differences explaining the variations in MT spacing observed in different species [1].  

To study MAP1B/Futsch, you will use inter-disciplinary experimental approaches that equip you with a wide range of skills relevant for the biomedical sciences and evolution biology. (a) To determine the precise sub-cellular localisation of MAP1B/Futsch you will use CRISPR/Cas9-mediated protein tagging and apply expansion/electron microscopy; molecular mechanisms will be determined via biochemical and in vitro assays. (b) To study MAP1B/Futsch family evolution you will use computational bioinformatics retrieving and analysing Futsch sequences from multiple species. (c) To determine the functional consequences of evolutionary variability you will generate hybrid proteins and assess their impacts on axon architecture.

The project will be supervised by experts in the field. Andreas Prokop has studied the Drosophila nervous system for 30 years, has long-standing experience with electron microscopy, and is also an expert in science communication (https://poppi62.wordpress.com/publications). Viki Allan studies MT-based transport with expertise in biochemical and in vitro assays to dissect functions of MT-associating proteins [Ref4]. Matthew Ronshaugen specialises on evolutionary biology and his lab is equipped to perform the computational analyses and generate CRISR/Cas9 variants [Ref5].

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website.

Funding Notes

Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References 1. Prokop, 2020, J Cell Biol 219, e201912081ff. — https://doi.org/10.1083/jcb.201912081
2. Prokop, 2021, Cytoskeleton 78, 52ff. — https://doi.org/10.1002/cm.21657
3. Hahn et al., 2019, Neural Dev 14, 10.1186/s13064ff. — https://doi.org/10.1186/s13064-019-0134-0
4. Korabel et al., 2018, PLoS One 13 e0207436 — https://doi.org/10.1371/journal.pone.0207436
5. Gallicchio et al., 2020, Genes|Genomes|Genetics 11 — https://doi.org/10.1093/g3journal/jkaa010

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