The zebrafish larva is an important model organism for investigation of complex in vivo physiological and pathological processes. Zebrafish larvae, up to 5 days post fertilisation (dpf) are approx. 4mm at 5 dpf and are NOT a protected organism at this developmental stage by UK and EU legislation. However, most of their biological processes, especially the innate inflammatory response, are fully developed as they possess key leucocytes (neutrophils and macrophages) and an intact and fully functioning cardiovascular system. Inflammatory processes, are directly responsible or involved in inflammatory diseases and virtually all known pathologies. Most researchers investigating inflammatory responses in vivo use mainly rodent models. Tissue repair, and where appropriate, tissue regeneration is a direct sequelae of resolving inflammation. The student will investigate, characterise and further optimise two zebrafish larval models that we have developed; (i) tailfin transection and (ii) laser-targeted injury or cryoinjury in the heart. Fish with fluorescently labelled immune cells [e.g., neutrophils (tg(mpx:EGFP)i114), eosinophils (tg(gata2:EGFP)) and macrophages (tg(MPEG1:mCherry))], endothelial cells (tg(Flk1:GFP)) and heart (tg(CMLC2:GFP)) to visualise and quantify inflammation and its resolution, together with measured tissue repair, cardiac function and regeneration. Incisive experiments will be performed to elucidate the role of granulocytes and macrophages on repair and regeneration. The student will build upon our work by driving granulocyte apoptosis to modify macrophage function to enhance inflammation resolution, and thereby promote tissue repair and regeneration. The major objective of this project is to make a major impact on the aims of the NC3Rs to replace, reduce and refine the use of animals for scientific purposes by elucidating in vivo inflammatory, repair and regeneration mechanisms using zebrafish larvae.
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