Background: Notch proteins are master regulators of cell fate during development and control cell renewal and differentiation in most adult tissues. Activation of Notch proteins is regulated by successive enzymatic cleavages that release the cell membrane-bound form that acts as a transcriptional regulator. More recently, import roles of intracellular vesicles in regulating Notch activity are being identified (see Pubmed 34572582). We have now identified metal-binding transporters (DMT1) as key mediators of intracellular Notch trafficking and activity.

Key objectives. To identify the importance of metal transport on intracellular Notch localization and activity in vesicles and how this can block Notch activity in tumours or promote regeneration of normal cell types. You will apply gain and loss of function (CRISPR, siRNA pharmacological) in Notch-dependent 2D and 3D models (cell lines, normal and tumour organoids (lung, intestine) and high-resolution fluorescent imaging (confocal, STED) and single-cell analysis to decipher how Dmt1/Notch signaling allocates cell identify and how iron transport is involved. You will use reagents we developed (Ab’s, Tg mouse models) to track the fate of Notch activity in fixed and live tissues.

We are looking for a Postdoc with a PhD in molecular and cell biology and a broad experience and track record with primary cell culture and cellular imaging using confocal fluorescence microscopy. You will be working in a team with a strong expertise in Notch biology.

General Profile: We are looking for an open-minded, independent and result-oriented scientist to join our team with a strong interested in fundamental research into regenerative medicine. You are fluent in English, both in writing and speech.

Fixed-term contract: 3 years.

The full-time position is offered for three years. The salary will be set in post-doc salary scale of the Collective Labor Agreement of the Dutch Universities (between €3.836,00 and €4.474,,00 gross per month depending on the level of experience). On top of this, there is an 8% holiday and an 8.3% year-end allowance.

The terms of employment of Maastricht University are set out in the Collective Labor Agreement of Dutch Universities (CAO), supplemented with local UM provisions. For more information look at the website www.maastrichtuniversity.nl > Support > UM employees.

Maastricht University

Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 20,000 students and 4,700 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Science and Engineering, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience. For more information, visit www.maastrichtuniversity.nl.

GROW Institute for Oncology and Developmental Biology

Maastricht University, GROW Institute for Oncology and Developmental Biology (www.grow-um.nl) . The radiotherapy department (www.maastrolab.com) conducts fundamental and translational research and is closely affiliated with 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 lab has four PI’s with research in the area of tumour cell metabolism (Kampen Group), Cell death (Bock group), Extracellular vesicles (Rouschop group) and Notch and Stem cells (Vooijs Group). In addition, we have established a strong expertise in culturing normal, and tumour stem cell models (organoids. ALI) and have access to a large tissue biobank and material from clinical studies. We have excellent high resoltuion optical microscopy and regenerative medicine.