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Structural analysis of clostridial toxins, their analogues and derivatives


   Department of Life Sciences

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  Prof Ravi Acharya  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

OVERVIEW

The PhD project will be aimed at elucidating the molecular structure of various Botulinum neurotoxin (BoNTs) molecules, more specifically the structural analysis of their domains, derivates and homologues, including analysis of complexes (e.g., receptors, substrates).

VALUE TO THE STUDENT

The project will provide high-level training in a broad set of skills:

  • Structure-function analysis using state of the art structural biology (X-ray crystallography, protein engineering and biophysical) tools and using the Diamond Synchrotron Facility.
  • Exposure to characterisation of ligand-protein interactions using bioinformatics and molecular modelling approaches.

With the rapidly expanding fields of structural molecular biology and bioinformatics, the project would provide the student with a valuable set of skills and working experience both in Academia (Department of Life Sciences, University of Bath) and Biopharmaceutical industry (Ipsen Bioinnovation Limited).

In addition, publications are strongly encouraged where possible (as an example, five recent references are listed in the References section below relating to recent successfully completed similar PhD work performed by Kyle Gregory).

Project keywords: structural biology; protein biochemistry; protein engineering; bioinformatics; botulinum neurotoxin; enzymology.

CANDIDATE REQUIREMENTS

Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent) in Biochemistry, Molecular Biology, Biophysics or Biology. A master’s level qualification would also be advantageous but not essential.

Non-UK applicants must meet our English language entry requirement.

ENQUIRIES AND APPLICATIONS

Informal enquiries are welcomed and should be directed to Prof Ravi Acharya on email address [Email Address Removed].

Formal applications should be submitted via the University of Bath’s online application form for a PhD in Biochemistry.

More information about applying for a PhD at Bath may be found on our website.

NOTE: Applications may close earlier than the advertised deadline if a suitable candidate is found. We therefore recommend that you contact Prof Acharya prior to applying and submit your formal application as early as possible.

FUNDING ELIGIBILITY

To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements: UK and Irish nationals (living in the UK or EEA/Switzerland), those with Indefinite Leave to Remain and EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme. This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.

EQUALITY, DIVERSITY AND INCLUSION

We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.


Funding Notes

The successful student will receive a PhD studentship funded by the project's industrial partner, Ipsen Biopharm Limited. The studentship will cover tuition fees at the 'Home' level and will provide a stipend at the applicable UKRI Doctoral Stipend rate (£18,622 in 2023/24, reviewed annually). There will also be a budget to cover consumables and training support.

References

1. Gregory KS, Acharya KR. A comprehensive structural analysis of Clostridium botulinum neurotoxin A cell-binding domain from different subtypes. Toxins (Basel). 2023 Jan 18;15(2):92. doi: 10.3390/toxins15020092.
2. Gregory KS, Newell AR, Mojanaga OO, Liu SM, Acharya KR. Crystal structures of the Clostridium botulinum neurotoxin A6 cell binding domain alone and in complex with GD1a reveal significant conformational flexibility. Int J Mol Sci. 2022 Aug 25;23(17):9620. doi: 10.3390/ijms23179620.
3. Gregory KS, Mahadeva TB, Liu SM, Acharya KR. Structural Features of Clostridium botulinum neurotoxin subtype A2 cell binding domain. Toxins (Basel). 2022 May 19;14(5):356. doi: 10.3390/toxins14050356.
4. Gregory KS, Mojanaga OO, Liu SM, Acharya KR. Crystal structures of botulinum neurotoxin subtypes A4 and A5 cell binding domains in complex with receptor ganglioside. Toxins (Basel). 2022 Feb 8;14(2):129. doi: 10.3390/toxins14020129.
5. Gregory KS, Liu SM, Acharya KR. Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co-receptor ganglioside. FEBS Open Bio. 2020 Mar;10(3):298-305. doi: 10.1002/2211-5463.12790.

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