Ruprecht-Karls-Universität Heidelberg
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Boutros0118 - Scientist (f/m) / PhD position
Project no:
Boutros0118

Project leader:

Project supervisor:
Boutros, Michael
Application deadline:
15. Sep 2018
Start of PhD project:
1. Oct 2018

Project description:

Title:
Single-cell analysis of stem maintenance and differentiation
Summary:
The PhD project will be focused on the systematic analysis of signaling pathways in the regulation of intestinal stem cells in Drosophila as model organism at the single cell level and comparative analysis in vertebrate systems. During homeostasis, the proliferation and differentiation of intestinal stem cells (ISC) in the Drosophila intestine is tightly controlled. In the past years, several conserved signaling pathways have been implicated in the regulation of ISC proliferation and differentiation decisions, including the Wnt, Notch, Hedgehog, Hippo and Dpp/BMP pathways. However, it remains still largely unclear how these different signaling pathways are orchestrated to control stem cell maintenance and differentiation decisions. In this project, we will analyze how different signaling pathways intersect to control maintenance of the epithelium and furthermore study how they impact transcriptional programs in ISCs and progenitor cells. The project should also perform a comparative analysis with vertebrate intestinal stem cells.
References:
Zhou J, Edgar BA, Boutros M (2017). ATF3 acts as a rheostat to control JNK signalling during intestinal regeneration. Nat Commun 8, 14289.
Augustin I, Dewi DL, Hundshammer J, Erdmann G, Kerr G, Boutros M (2017). Autocrine Wnt regulates the survival and genomic stability of embryonic stem cells. Sci Signal 10, eaah6829.
Methods that will be used:
The project will use single-cell sequencing techniques to understand in more detail how signaling pathways influence gene regulatory circuits in the Drosophila intestine during homeostasis. Single-cell transcriptome analysis after perturbation of selected components will be performed. Furthermore, candidate genes identified in a genome-scale in vivo Drosophila screen will be characterized using methods like RNAi and CRISPR/Cas9.
Cooperation partners:
This project will be part of the SFB 873 “Maintenance and differentiation of stem cells in development and disease“.
Personal qualifications:
Applicants should hold a diploma/masters’ degree in biology/life sciences with an excellent background in cell biology or biochemistry and have strong laboratory, analytical and communication skills. The candidate should be enthusiastic, motivated, result-driven, and have a critical personality. The student should have good organization, writing and communication skills and be able to work well both independently and in a team environment.
Keywords:
Stem cells, signaling pathways, single-cell analysis, Drosophila