This is a highly interdisciplinary project that involves fluorescent probe development, macrophage cell biology and in vivo imaging. The main goal of the project is to develop and validate novel fluorescent smartprobes to image macrophages in vivo. Macrophages (and their precursors, monocytes) are the 'big eaters' of the immune system. Macrophages are remarkably plastic and can change their functional phenotype depending on the environmental cues they receive. Through their ability to clear pathogens and instruct other immune cells, these cells have a central role in protecting the host but also contribute to the pathogenesis of inflammatory and degenerative diseases. The specific roles of macrophages in many microenvironments remain elusive because of the lack of technologies to target these unique populations of cells in vivo. Therefore, it is imperative that new chemical probes specifically targeting macrophages are developed. We work in the development of smartprobes targeting intracellular processes in macrophages (e.g. phagosomal acidification (PhagoGreen-Figure below), generation of reactive oxygen species, hCE-1 esterase activity, among others) so that they emit fluorescence only inside macrophages. The probes will be optimised to image live mouse and human macrophages, and to ensure they do not alter the normal physiology of the cells. Finally, selected optimal probes will be validated in relevant animal models (e.g. LPS-induced acute lung injury (alveolar macrophages), thioglycollate-induced peritonitis (peritoneal macrophages)) and in different in vivo imaging platforms.
|Effective start/end date||1/09/15 → …|