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Identifying host factors involved in staphylococcal infection (STAPHYLOMICS)
Start date: 01 Feb 2015, End date: 31 Jan 2017 PROJECT  FINISHED 

"Staphylococcus aureus is able to cause a wide range of diseases, with no vaccine available and common antibiotic resistance. It is therefore essential to better understand S. aureus pathogenesis. Accumulating evidence indicates that an intracellular infection stage is an important step in the disease progression. However, the mechanism of S. aureus phagocyte parasitism is currently unknown. A key question now arises as to what genes are triggered within phagocytes in response to S. aureus internalisation, which promote the creation of a favourable intraphagocyte environment. The host institution has pioneered cutting-edge technology, where specific phagocytes recovered from zebrafish larvae infected with other pathogens are subjected to transcriptomic analysis by RNA sequencing. I, on the other hand, have extensive experience in studying S. aureus infection using zebrafish. Thus the proposed project will be a great synergy between me and the host laboratory, whilst providing myself with world class training. I will perform an in vivo analysis of transcriptomes of infected macrophages and neutrophils using zebrafish larvae with these cell types specifically labelled. The infected phagocytes will be obtained using fluorescence-activated cell sorting technology. Transcriptomes will be then determined by RNA sequencing and bioinformatics analyses. A set of candidate genes will be short listed followed by functional studies via a loss-of-function, morpholino-mediated approach. Several aspects of staphylococcal infection will be tested on morphants to determine the importance of preselected host genes in S. aureus phagocyte subversion. The project will generate important fundamental data on S. aureus disease mechanisms and provide new insights into finding potential strategies to treat staphylococcal infections. This fellowship will give me an ideal platform for my subsequent reintegration in my own country as a mature and successful scientist on the international stage."
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