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Structural and biological characterisation of virulence factor in Gram-negative pathogens affecting aquaculture


   Institute of Aquaculture

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  Dr Andrew Desbois  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Gram-negative pathogens are responsible for major disease problems in humans and animals, and a better understanding of the mechanisms for how these bacteria cause infections is key to identifying more effective ways to prevent and treat outbreaks. Vibrio spp. are particularly problematic in aquaculture systems, where fish and shellfish are farmed primarily for human consumption. Indeed, Vibrio spp. are the aetiological agents of several important global diseases such as vibriosis of fish and acute hepatopancreatic necrosis disease (AHPND) of shrimp, while some species are zoonotic thus posing risks to humans, including V. parahaemolyticus, V. vulnificus and V. cholerae[1,2].

In earlier work with a transposon mutant library of Vibrio anguillarum (an important marine pathogen of fish and invertebrates), we identified a transformant with highly attenuated virulence in a novel insect alternative model of infection [3]. This mutant was disrupted in a gene not previously known to play a role in infection. Further investigation has revealed the disrupted gene to encode a protein with toxic action that appears to be activated by an enzyme, which allows for its release from the bacterium into the infected host. These components represent potential vaccine candidates and drug targets for new prophylactic (e.g., vaccine) and therapeutic approaches.

The aim of this project will be to characterise the structure and biological activities of the novel protein and its activator to assess the role of these proteins in bacterial virulence. This will be achieved by: expressing the genes of interest in an heterologous host; isolating and purifying the proteins of interest; determining the structures of the proteins and their interaction; assessing the biological activity of the activated protein, including against fish cell lines.

In this fundamental life science project with practical applications, the successful candidate will be trained in microbiology including gene cloning and heterologous expression; protein biochemistry, structural biology and crystallography; and fish cell culture and bioassay development. The student will receive a diverse programme of skills development co-ordinated by the Institute of Advanced Studies (Stirling) and the EASTBIO network to enhance future employability prospects. The student will split their studies between the Universities of St Andrews and Stirling depending on the needs of the different project components.

Application Procedure:

To apply for an EASTBIO PhD studentship, follow the instructions below:

Check the details of this project on FindaPhD and contact the lead supervisor Dr Andrew Desbois, [Email Address Removed] before you apply.

After you have discussed the project, complete our Equality, Diversity and Inclusion survey (Equality, Diversity and Inclusion survey) and then fill in the EASTBIO application form (noting that the application date on the form differs from the actual date of 15th June 2022) and submit your completed EASTBIO application form, along with academic transcripts to

Send EASTBIO Reference Form to your two academic/professional referees, and ask them to submit as specified on the project adverts.

If you have further queries about the application/recruitment process please email Dr Andrew Desbois, [Email Address Removed].

Please ask your referees to submit your references directly to Dr Andrew Desbois, [Email Address Removed]

Unfortunately, due to workload constraints, we cannot consider incomplete applications


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (http://www.eastscotbiodtp.ac.uk/), with projects envisaged to commence in Sept/Oct 2022.
This opportunity is open to home/UK candidates (including EU nationals that hold UK settled or pre-settled status) and provides funding to cover a stipend and tuition fees. Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

References

[1] de Souza Valente and Wan (2021) https://doi.org/10.1016/j.jip.2020.107527
[2] Ina-Salwany et al 2019 https://doi.org/10.1002/aah.10045
[3] McMillan et al. (2015) https://doi.org/10.1186/s12866-015-0466-9
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