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Bio-engineering botulinum toxin to repair damaged nerve cells

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  • Full or part time
    Prof J M Henley
    Prof DN Woolfson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Botulinum toxins (BoNTs) are some the deadliest poisons known. Their main action is to prevent neurotransmitter release by enzymatically destroying the activity of an essential presynaptic protein called SNAP-25. BoNTs have a heavy chain, which is required for the intracellular delivery of the toxin, and a light chain, which is the catalytic effector. Beyond their toxicity there are many intriguing questions about i) how BoNTs get into neurons, ii) how the individual peptides can remain stable and active for many months in the constantly changing environment of the synapse, and iii) other non-toxic effects of BoNTs, especially the cell growth promoting effects of the heavy chain.

Building on an emerging literature and our extensive preliminary data, the aims of this PhD are to investigate the molecular basis of the positive actions of the heavy chain of BoNT/A (BoNT/A HC) on promoting neuronal differentiation and morphology. It is important to emphasize that BoNT/A HC has no catalytic activity and is not toxic, so there are no safety concerns or restrictions on the work to be performed. In the first instance this project will use in vitro cell culture systems and the specific objectives will be to:

1. Characterise the neurotrophic actions of BoNT/A HC using fixed and live cell confocal imaging.
2. Investigate the minimal structural requirements of BoNT/A HC to produce these effects.
3. Define the upstream pathways and downstream effectors involved.
4. Determine if the neurotrophic actions of BoNT/A HC can ‘rescue’ stressed cells in models of neuronal damage and/or degeneration.

Addressing these questions will make significant contributions to the fundamental understanding of BoNT biology. Furthermore, the results obtained could have tremendous potential to guide future efforts to bioengineer modified forms of BoNT/A HC with enhanced repair/regenerative properties for the treatment of pathways damaged by trauma, stroke and neurodegeneration.

Funding Notes

Please refer to the following pages on how to apply and eligibility:


Henley JM, Craig TJ and Wilkinson KA Neuronal SUMOylation: Mechanisms, Physiology, and Roles in Neuronal Dysfunction (2014) Physiol. Rev. 94, 1249-1285. PMID: 25287864

Guo C, Hildick KL, Luo J, Dearden L, Wilkinson KA and Henley JM (2013) SENP3-mediated DeSUMOylation of dynamin-related protein 1 Promotes Cell Death Following Ischemia. EMBO J. 32(11) 1514-28. PMID: 23524851

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