Ruprecht-Karls-Universität Heidelberg
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Boutros0218 - Scientist (f/m) / PhD position
Project no:
Boutros0218

Project leader:

Project supervisor:
Boutros, Michael
Application deadline:
15. Sep 2018
Start of PhD project:
1. Oct 2019

Project description:

Title:
Dissecting Wnt signalling in melanoma using CRISPR/Cas9 screens
Summary:
Wnt signaling is a key regulatory cascade during development, homeostasis and various tumor entities. In the past years, Wnt signaling has been implicated in the progression and metastasis of melanoma. Normal skin and benign nevi express several canonical and non-canonical Wnt proteins which are downregulated in melanoma. A decrease of canonical Wnt signaling has also been correlated with a poor outcome. The PhD project will establish image-based assays using CRISPR/Cas9 methodologies to monitor endogenous Wnt pathway activity and downstream effects for genetic and small molecule screening. Modulators of Wnt signaling and their phenotypes will be identified in melanoma, as well as novel targets for tumor-immune cell interactions.
References:
Breinig M, Klein FA, Huber W, Boutros M: A chemical-genetic interaction map of small molecules using high-throughput imaging in cancer cells. Mol Syst Biol. 11: 846, 2015

Boutros M, Heigwer F, Laufer C: Microscopy-Based High-Content Screening. Cell. 163: 1314-25, 2015

Glaeser K, Urban M, Fenech E, Voloshanenko O, Kranz D, Lari F, Christianson JC, Boutros M: ERAD-dependent control of the Wnt secretory factor Evi. EMBO J. 37, 2018
Methods that will be used:
The project will generate endogenously tagged key regulators of the Wnt signaling pathway and melanoma specific target and effector genes. Existing assays to measure the effect of autocrine and paracrine Wnt secretion on cell migration and cell adhesion processes using image-based methods will be transferred in a high-throughput screenable format.
Cooperation partners:
This project will be part of the GRK 2099 “Hallmarks of Skin Cancer”.
Personal qualifications:
Applicants should hold a diploma/masters’ degree in biology /life sciences with an excellent background in cell biology, biochemistry or biotechnology 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 excellent organization, writing and communication skills and be able to work well both independently and in a team environment.
Keywords:
Wnt signaling, melanoma, tumor-immune cell interaction