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Can genome engineering be used to resist diseases currently reducing biodiversity?

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Project Description

This project tests if genome engineering techniques can increase resistance of frogs to chytridiomycosis caused by Bd, which causes extinctions. Whole genome data identified changes enriched in populations frogs surviving extinction level pathogen exposure. These are limited to the MHC genes; they also express different antimicrobial peptides to susceptible frogs.

First X. tropicalis, a Bd-susceptible frog, will be altered to have MHC sequences and antimicrobial peptides typical of a Bd-resistant frog. Genome engineering used at EXRC will alter the MHC genes. To express antimicrobial peptides, we have successfully tested the DNA sequences expressing GFP trangenically in the secretory glands of X. tropicalis. The tools and techniques are in place to enable the student to learn and execute sophisticated genome engineering to produce a frog that we hypothesise is disease resistant.

The project then tests whether the genetically altered frog is resistant; IOZ has facilities and expertise to expose the frogs to pathogens. In addition to comparing the ability of the GA frogs to resist Bd with that of wild-types the reproduction, growth and other traits will be measured, testing whether the genetic alteration has a fitness cost. If the genetically altered animals resist Bd without costs to their fitness, this will act as proof of principle that genetic alteration of animals threatened by a pathogen may be a viable mechanism for retaining biodiversity, albeit as a last resort.

Research themes
Project Specific Training

Training will be delivered by the supervisory team, their senior animal technologists and post-docs at either the EXRC or IOZ.

• PIL under ASPA (external, Red Kite Vets)
• Care of Xenopus, breeding and raising embryos (internal, EXRC)
• Bioinformatic design of genome editing experiments (internal, EXRC)
• Molecular biology – making genome editing constructs (internal, EXRC)
• Genetic alteration of Xenopus embryos (internal, EXRC)
• Genotyping of Xenopus embryos (internal, EXRC)
• Challenge experiments with Bd infection (Internal, IOZ)
• Analysis of pathogen loads by RT qPCR (internal, IOZ)
• Survival and fitness assays (internal, IOZ) 
• Statistical analysis of fitness results (internal, IOZ) 

Potential Career Trajectory

The variety of techniques that will be applied during this project will suit the student for any post requiring complex molecular genetics and genome engineering skills including a biomedical career, the other project elements will prepare the graduate for careers in conservation science in addition to regulatory roles and study of pathogens (wildlife or otherwise). 

Project supervisor/s
Matt Guille
School of Environmental and Life Sciences
Portsmouth
matthew.guille@port.ac.uk
Trenton WJ Garner
Institute of Zoology, ZSL
IoZ
trent.garner@ioz.ac.uk
Supervision balance
60:40