The group of Marc Vooijs aims to unravel the tissue and context-specific regulation of Notch family proteins during normal tissue homeostasis and in cancer cells. Notch proteins are master regulators of cell fate during development and control self-renewal and differentiation in most adult tissues. Activation of Notch proteins is regulated by ligand binding leading to successive enzymatic cleavages that release the cell membrane-bound form of the receptor that acts as a transcriptional regulator. Notch activity is also regulated by intracellular trafficking in vesicles but how localization, degradation, and activity are connected is unclear. We recently identified an ion and metal-binding transporter as a novel key mediator of Notch receptor localization, trafficking, and activity. The overall aim of the Notch group is to identify actionable targets in the Notch signalling cascade that can be used to target cancers or to promote tissue regeneration.
Your work will be aimed at characterizing the role of one of these metal transporters in Notch regulation using in vitro cell models and tissues. The key objectives of our work are 1) To identify the importance of transport(er) in Notch receptor localization, vesicular trafficking and transcriptional activity and 2) to interfere with the function of transport to modulate Notch activity to direct cell differentiation or promote self-renewal in normal and cancer cells. You will apply gain and loss of function in Notch-dependent 2D and 3D models ((stem) cell lines, organoids), conduct gene expression and protein analysis (qPCR, WB, IP) and use high-resolution imaging (Confocal, STED, EM) and tissue expression analysis to decipher how Notch receptor transport in cells influences the spatial and temporal Notch activity to direct cell differentiation and cell renewal.
Maastricht University, GROW Institute for Oncology. At the department of Radiotherapy, we conduct fundamental and translational research and are affiliated with the MAASTRO patient clinic and the Maastricht Comprehensive Cancer Centre. Our research is focused on identifying therapeutic vulnerabilities in the tumour microenvironment to improve treatment response. The department has four PI led groups with research themes in tumour cell metabolism, cell death, extracellular vesicles and Notch signaling and stem cell fate. The lab has strong expertise in culturing normal and tumour stem cell models (organoids, other 3D models) and has access to a large tissue biobank and material from (pre)clinical studies. Furthermore, we have core facilities for NextGen sequencing, iPSC, high resolution optical and electron microscopy and mass spectrometry (M4I) at UM.
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