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BBSRC White Rose CASE DTP Studentship - Developing novel inhibitors of unconventional secretion based on Botulinum based therapeutics

   School of Biosciences

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  Dr A Peden, Dr M Elliott  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Unconventional secretion is a fundamental cellular process which not only underpins normal physiology but is a key driver in chronic inflammation and cancer. At present we have a limited molecular and mechanistic understanding of this process. The aim of this project is to use Botulinum based molecules to elucidate the role of SNARE proteins in unconventional secretion. The knowledge generated from this project in the longer term will provide a platform for the development of novel inhibitors of this pathway.

Clostridial neurotoxins are produced by anaerobic bacteria such as Clostridium botulinum. Each toxin molecule has a highly conserved zinc-dependent protease domain that specifically cleaves SNARE proteins, a family of molecules required for intracellular trafficking and vesicle fusion. This project will make use of a library of novel toxin molecules to identify and characterise the role of SNARE proteins in the biogenesis and fusion of unconventional secretory carriers with the cell surface.

The student will be trained in a range of state of the art techniques including recombinant protein engineering, super resolution imaging and quantitative secretion assays. In addition, the student will also gain experience in approaches such as molecular biology, cell culture, viral transductions and flow cytometry.

The project is a collaboration between the University of Sheffield and the pharmaceutical company Ipsen so the student is expected to spend up to 6 months at the company. The studentship is very well funded and has an annual stipend enhancement of £3,500 and up to £12,000 placement expenses.

The BBSRC WR DTP and the University of Sheffield are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Note: Relocation costs for international students to the UK (visa, insurance, NHS fees, flights, etc) will be the responsibility of the student 

 Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. 

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Programme: PhD in Mechanistic Biology (4 years)

Start Date: 1st October 2023

Funding Notes

This project is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. Appointed candidates will be fully-funded for 4 years. The funding includes:
• Tax-free annual UKRI stipend (£17,668 for 2022 starts)
• UK tuition fees (£4,596 for 2022)
• Research support and training grant (RSTG)
We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries 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


Gordon D.E., Shun-Shion A.S., Asnawi A.W., Peden A.A. Quantitative Flow Cytometry-Based Assays for Measuring Constitutive Secretion. 2021 Methods in Molecular Biology. DOI: 10.1007/978-1-0716-1044-2_8.
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

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