Stem Cells and Organoid Biology

ESR project

1.2

Title of project

Modulating Wnt signaling responses in stem cells and cancer

We offer

A 4-year PhD student position in the interdisciplinary area of regenerative medicine. Your project will focus on the design, development and evaluation of peptide-based biologicals that modulate Wnt signaling responses in stem cells and cancer.

We ask

You hold a Master’s degree in molecular and cellular life sciences or in a related area. You have affinity with mechanisms of cellular signal transduction and thrive in a multidisciplinary research environment. Experience with structural biology approaches or protein engineering are of benefit.

Department

The lab of Madelon Maurice focuses on the mechanisms of signaling in stem cells, development and cancer. The lab is embedded in a dynamic and highly interactive research environment with international research groups and direct access to a large number of facilities. Local training opportunities include molecular cell biology, biochemistry, advanced imaging and genomics technologies. See also: and http://cellbiology-utrecht.nl/ and http://www.umcutrecht.nl/en/Research/Research-centers/Center-for-Molecular-Medicine/Section-Cell-Biology.

Description

Wnt proteins comprise a family of conserved, secreted glycolipoproteins that control the maintenance and proliferation of stem cell reservoirs during adult tissue renewal and regeneration after injury. Deregulated Wnt signaling due to mutations is strongly linked to cancer and degenerative disease. The responsiveness of stem cells to Wnt is tightly regulated by positive and negative feedback regulators that control Wnt receptor availability and activity. The ESR will embark on a project that aims to design innovative tools and methods to manipulate Wnt receptor activity in stem and cancer cells. The ESR will combine peptide-based reagents and protein engineering to modulate protein activity at the cell surface (collaboration Pepscan and Friedler). The ESR will map protein interaction sites of the developed reagents and employ advanced imaging and biochemical assays to determine consequences for receptor trafficking and turnover. The ESR will investigate how manipulation of Wnt receptor activity affects stem cell compartments as well as lineage decisions in complex tissues, using both healthy and patient-derived tumor organoids of different tissue origin. In summary, the ESR will be trained as a multidisciplinary scientist with know-how in protein engineering, biochemistry, imaging and applications in organoid technology.

Requirements

  • You have a Master in molecular and cellular life sciences or in a related area.
  • You have affinity with cellular signal transduction and are challenged by molecular mechanistic research questions.
  • You are a team player, highly motivated and thrive in a multidisciplinary environment.
  • Experience with structural biology or protein engineering are of benefit.

Contact person & more information

Prof. dr. Madelon Maurice, UMC Utrecht
m.m.maurice@umcutrecht.nl

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information