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Project

Elucidating the molecular dynamics of mammary tissue remodeling and tumor initiation using multiplexed biosensors in a novel branched mammary organoid system.

The mammary gland is a branched organ that undergoes extensive remodeling throughout life. This remarkable regenerative ability of the mammary gland comes at a cost, as the extensive changes in proliferation and tissue architecture are also at the basis of progressive accumulation of oncogenic mutations. Although morphologically well described, the molecular pathways driving these morphological and functional changes are still poorly understood. Organoid models are a powerful tool to gain insights into tissue morphogenesis. However, current available mammary organoid culture protocols result in morphologically simple structures that do not resemble the branched morphology of the in vivo mammary gland. To study dynamic mammary gland remodeling at the molecular level, I developed a protocol to obtain complex branched mammary organoids that enable ex vivo optical monitoring of branching and remodeling events. To unravel the molecular signaling pathways driving mammary gland remodeling, I will combine this novel organoid model with multiplexed signaling reporters and timelapse microscopy. I will challenge the system by introducing sporadic loss of BRCA1, an oncogenic driver in the mammary gland, to elucidate the molecular dynamics that drive mammary tumor initiation. Using the dynamic readouts from the multiplexed signaling biosensors in the complex mammary organoids I will build a 4D map of dynamic signaling during mammary gland remodeling and tumor initiation.

Date:15 Apr 2022 →  Today
Keywords:signaling biosensors, branching morphogenesis, tumor initiation, mammary gland
Disciplines:Cancer biology
Project type:PhD project