EASTBIO: The role of post-translational modifications in the fish immune response to viral diseases at the University of Edinburgh

Supervisors:  Dr Diego Robledo, Prof Ross Houston, Prof Samuel Martin, Beatriz Orosa.

Aquaculture is the fastest growing food industry worldwide, playing a critical role in feeding the world without exhausting oceans natural resources. However, infectious diseases pose a constant risk to animal welfare and food security. Viral pathogens are currently the main threat to aquaculture sustainability, with limited prevention or treatment options. In this context, improvement of fish disease resistance, including vaccine development, selective breeding and genome editing, constitute the best approach to tackle viral diseases in aquaculture (Houston et al. 2020 Nat Rev Genet 21:389-409).

Post-translational modifications (the attachment of ubiquitin and ubiquitin-like molecules to proteins) regulate virtually all aspects of the immune response, from pathogen recognition to the activation of adaptive immunity via antigen presentation. In parallel, pathogens such as the Influenza virus have evolved mechanisms to manipulate the ubiquitin system. To avoid the host immune response Influenza interacts directly with the human TRIM25 E3 ubiquitin ligase, which is responsible for the activation of the interferon pathway in mammals, key for a successful immune response. Our previous research in Atlantic salmon and common carp (e.g. Palaiokostas et al. 2018 G3 8:3507-3513) suggests that TRIM25 genes may also play an important role in resistance to viral diseases in fish. However, there are between 15 and 1000 copies of this gene in fish species, pointing towards a huge functional diversification. While we know several of these copies are involved in immunity (Langevin et al. 2019 Fish Shellfish Immunol 86:724-733), their specific function is unknown. 

The main aim of this project in to understand the role of posttranslational modifications in the immune response to viral diseases in Atlantic salmon, paying particular attention to TRIM25-like genes and Infectious Salmon Anaemia Virus (ISAV), an orthomyxovirus related to Influenza. This 4-year studentship will provide an excellent inter-disciplinary training opportunity, covering aspects of genomics and genetics, molecular biology, virology and bioinformatics, and applying a wide variety of techniques such as CRISPR/Cas9 genome editing, RNA sequencing, protein immunoprecipitations and mass spectrometry. The student will be part of a large multidisciplinary and diverse team working in aquaculture genetics at the University of Edinburgh (https://www.ed.ac.uk/roslin/aquaculture), in close collaboration with world experts in fish immunology at the University of Aberdeen (https://www.abdn.ac.uk/sfirc/) and Zoetis (http://www.zoetis.com/). The partnership with Zoetis as part of the CASE studentship offers an exciting opportunity for the PhD student to work on the interface between basic research and commercial application, and to gain first-hand experience outside academia.

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0 .

EASTBIO Application and Reference Forms can be downloaded via   http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [email protected]

You should also ensure that two references have been send to [email protected]  by the deadline using the EASTBIO Reference Form.

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees.  The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees.  There is a cap on the number of international students the DTP recruits.  It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our university.

Please refer to UKRI websiteand Annex B of the UKRI Training Grant Terms and Conditionsfor full eligibility criteria.

Closing Date: 16th December 2021