Stem Cells and Organoid Biology

ESR project

1.8

Title of Project

Personalized medicine for patients with congenital intestinal disease.

We offer

A 4-year PhD student position in the interdisciplinary area of regenerative medicine. Your project will focus on generating patient-derived intestinal organoid cultures to study pathophysiology of congenital intestinal diseases and develop an organoid-based screening platform for personalized medicine.

We ask

  • You hold a Master’s degree in cellular biology, molecular biology, biomedical sciences or in a related area.
  • You have affinity with advanced cell and tissue culture techniques and molecular biology techniques and thrive in a multidisciplinary research environment.
  • Experience with organoid and gene editing technologies are of benefit.

Department

The Department of Pediatric Gastroenterology at Wilhelmina Childrens’ Hospital - UMC Utrecht and RMCU

Description

The process of distribution of transporters and enzymes at the luminal (apical) membrane of intestinal epithelial cells is essential for efficient digestion and absorption of nutrients. Congenital defects in this process can cause severe neonatal diarrhea with high risk of dehydration and eventually death. Most patients with congenital diarrheal disorders (CDD) are life-long dependent on intravenous nutrition unless treated by intestinal transplantation. Unravelling disease mechanisms of CDD imposes a great challenge in the field as it is currently unknown how defects in intracellular trafficking or digestion lead to life-threatening diarrhea.

The group of Sabine Middendorp focuses to understand the disease-causing molecular mechanism in patients with CDD and to develop targeted diagnostic and therapeutic options. For this, we use human ex-vivo stem cell-derived organoids as an in vitro model system to elucidate the pathophysiology of disease. We combine organoid technology with system-wide approaches, such as RNA-seq and targeted approaches, such as CRISPR/Cas9 mediated knockout technology.

This project aims to better understand physiology of the human gut and the consequences of genetic defects underlying congenital diarrheal diseases (CDD). To dissect the molecular mechanism of CDD, we will identify gene defects in patients, develop functional assays to determine their physiological effect and develop an organoid-based screening platform for personalized medicine that restores the phenotype.

Requirements

  • You have a Master in cellular, molecular biology, biomedical sciences or in a related area You have affinity with advanced cell and tissue culture techniques and molecular biology techniques
  • You are a proactive person, an independent thinker and a team player with communication skills and very good command of English.
  • Experience with organoid and gene editing technologies are of benefit

Contact person & more information

Dr. Sabine Middendorp
s.middendorp@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