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The main goals of the selected Ph.D. candidate will be to:
1) Visualize exosomes targeting and crossing of the endothelial barrier
2) Determine the functional effects of exosome uptake on endothelial function
3) Identify the molecular mechanisms involved using multi-omics approaches
Nr of positions available : 1
Our team studies the molecular and biomechanical events underlying tumor invasion, angiogenesis and metastasis. To this end, we are using a combination of models ranging from in vitro cell biology and biophysical assays (Goetz et al., Cell, 2011) to in vivo animal models of tumor progression (mice and zebrafish) (Goetz et al., Cell Reports, 2014). In particular, we are developing intravital imaging and intravital CLEM (Correlated Light and Electron Microscopy) technologies for tracking subcellular events in vivo at high-resolution (Karreman et al. PloS One 2014; Karreman et al., Journal of Cell Science, 2016). This development is performed in close collaboration with Y.SCHWAB (EMBL, Heidelberg). More recently, our team was involved in the identification of a new molecular driver of exosome biogenesis (Hyenne et al., Journal of Cell Biology, 2015).
Exosomes are small extracellular vesicles secreted by most cells, circulating in all body fluids and containing proteins and RNAs (mRNAs, miRNAs). They are emerging as novel contributors to tumor progression and metastasis by mediating communication between tumor and stromal cells. Notably, tumor-secreted exosomes drive the formation of a premetastatic niche in a distant organ, thereby favouring the seeding of invasive tumor cells. To do so, exosomes need to cross the endothelial barrier, affect its permeability and indoctrinate local stromal cells through mechanisms that remain largely unknown. We have recently identified new genes required for exosome secretion in mammalian tumor cells (Hyenne et al., JCB, 2015). We are now developing tools allowing us to follow exosomes in a living animal (either using genetically encoded fluorescent proteins, or through dye labelling of exosomes) and, in parallel, we are characterizing the content of tumor exosomes.