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BBSRC White Rose DTP iCASE - Exploring the therapeutic potential of BoNT/X

  • Full or part time
  • Application Deadline
    Monday, January 06, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Clostridial neurotoxins are produced by anaerobic bacteria such as Clostridium botulinum. Each toxin molecule has a highly conserved zinc-dependent protease domain that has exquisite specificity for SNARE proteins, a family of molecules required for intracellular trafficking and vesicle fusion. Due to their potency, specificity and length of action they have become widely used in the cosmetic industry and have also proven very effective in the treatment of medical disorders associated with neuronal hyperactivity. Through the sequencing of environmental samples several new toxins have recently been discovered which cleave SNARE molecules not involved in neurotransmitter release so potentially opening up the possibility of targeting new biological processes and medical conditions.

The goal of this project is to characterise the biology of BoNT/X and determine which intracellular pathways it inhibits so gaining an insight into its therapeutic potential. The student will be trained in a range of state of the art techniques including recombinant protein engineering, super resolution microscopy and intracellular transport assays. In addition, the student will also gain experience in generic approaches such as molecular biology, cell culture and viral transductions. As this project is a collaboration between the University of Sheffield and the pharmaceutical company Ipsen, the student will spend a significant period of time based with the company.

Funding Notes

preferred start date October 2020
- a tax-free stipend at the standard Research Council rate (~£15,009, to be confirmed for 2020) for 4 years
- tuition fees at the UK/EU rate for 4 years.
- research costs
At least a 2:1 honours degree in a relevant subject or equivalent is required.
Studentships are available to UK and EU students who meet the UK residency requirements.

For further information on the host lab, see View Website
Informal enquiries to:

References

Gordon D.E., Chia J., Jayawardena K., Antrobus R., Bard F., Peden A.A. VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane.2017 PLoS Genetics. doi:10.1371/journal.pgen.1006698.

Fonfria E., Elliott M., Beard M, Chaddock J.A. and Krupp J. Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity. 2018 Toxins. doi: 10.3390/toxins10070278

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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