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Kyle Buchan

Email:                   kdbuchan1@sheffield.ac.uk
​PhD:                      2014-2018
Department: Infection, Immunity & Cardiovascular Disease
Supervisor(s): 
Prof. Steve Renshaw (IICD) 
                                 
Prof. Simon Foster (MBB)
​Project: Building an improved model for Staphylococcus aureus infection by humanising components of the Zebrafish immune system

​Staphylococcus aureus is one of the most important pathogens facing the world today. So far, much of our understanding of how S. aureus causes disease has been derived from experiments using infection models such as rabbits, rats and mice; however, these models can only offer so much without fully representing a typical human infection. Recently it has been found that many of the virulence factors produced by S. aureus are only active within humans, meaning that any infection model lacking the targets of these factors cannot account for their role during infection. The Zebrafish (Danio rerio) is already an established model in developmental biology and immunology research, with many tools and techniques readily available for working with them, facilitated by their genetic tractability. As well as being amenable to imaging and reproducible in high-throughput, Zebrafish have an immune system that is closely similar to humans, making it already a more suitable model for the study of infection over existing models. The project will aim to create transgenic lines of Zebrafish which express these human components that are specifically targeted by S. aureus; these lines can then be dissected with high resolution to determine some of the roles that these factors play in shaping a S. aureus infection.

Context: Existing models for studying infection by S. aureus do not sufficiently represent a normal human infection of this pathogen. Since an ideal model does not exist, the project proposes to build this model, using the Zebrafish as a ‘chassis’ that contains and expresses human components. These ‘humanised Zebrafish’ would greatly facilitate the investigation of the functions of major virulence factors, whose roles during infection have until now have not been possible to study during the infection process.
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The University of Sheffield 
Western Bank 
Sheffield, South Yorkshire 
S10 2TN 

United Kingdom
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