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Expression of recombinant antibodies in microalgae: from proof of concept to potential treatment for the aquaculture sector.

University of Exeter - College of Life and Environmental Sciences.

Qualification Type: PhD
Location: Exeter
Funding for: UK Students, EU Students
Funding amount: BBSRC SWBio DTP funded CASE studentship available for September 2022 entry. The studentship will provide funding of fees and a stipend which is currently £15,609 per annum for 2022-23, on a full time basis.
Hours: Full Time
Placed On: 22nd October 2021
Closes: 6th December 2021
Reference: 4285

Shrimp is one of the most valuable seafood products, representing a market of £20 billion per year. Around 55 % of the global shrimp production comes from farming, which generates valuable incomes in many countries.  

However, emerging infectious disease threaten this industry; pathogens such as the bacterium Vibrio parahaemolyticus cause hepatopancreatic necrosis disease (AHPND) by developing in the digestive tract of farmed shrimps and secreting toxins. Currently, solutions to control the spread of infection in aquacultures are limited to water disinfection using antibiotics or ozone, or providing antibacterial plant extracts, immunostimulants, and probiotics food supplements to the crustaceans -mainly bacteria and microalgae. None of those techniques is both sustainable and very efficient. 

So far, the most conclusive solution to limit V. parahaemolyticus infections consists of inducing a passive immunisation of shrimp by adding anti-Vibrio antibodies to their food. These tests are currently still at the research stage. In one study, antibodies were generated by infecting a fish with the vibrio’s toxin. Following infections, the gene sequences encoding the antibodies were isolated and transformed into Human Embryonic Kidney (HEK) cell platforms. Antibodies were then produced by those HEK cells cultured in bioreactors, purified, and added to the shrimp food pellets. This approach is not economically viable when scaled up. However, this antibody could be produced and delivered directly within a microalga. This would be an ideal alternative since microalgae have two major advantages: they require inexpensive growth conditions, and several species can be used to produce recombinant proteins.    

This project consists in producing fish antibodies in microalgae and show how microalgal synthetic biology can lead to new treatment solutions for the aquaculture sector.    Various genetic sequences of a previously characterised anti-Vibrio antibody will be cloned into DNA constructs for transformation in microalgae. Several new signal peptides will be identified using bioinformatic methods in order to address the antibody localisation within specific cellular compartments. The antibody’s affinity towards its target will be measured from microalgal crude extracts and after purification, to compare with the HEK cells’ version. Once the most suitable clones are identified, similar analysis will be reproduced after scaling up the cultures and freeze-drying the cells. 

Upon completion of this PhD, the applicant can expect to have created a new cell platform that can be used for shrimp treatment trials. They will also have developed various molecular tools and methods that will be shared with the microalgae research community. 

Eligibility 

To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria. 

A fully-funded four year SWBio DTP studentship will cover 

  • a stipend* at the standard Research Council UK rate; currently £15,609 per annum for 2022-23
    •    research and training costs 
    •    tuition fees (at the standard Research Councils UK rate) 
    •    additional funds to support fieldwork, conferences and a 3-month internship 

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.  Any further queries in relation to residency must be directed to the institution. 

* An enhanced stipend is available for students with a recognised veterinary degree qualification (£24,090 per annum for 2022--2023). There may also be enhanced stipends associated with projects that have a CASE partner (highlighted as *CASE in the project lists). 

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