Ruprecht-Karls-Universität Heidelberg
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Acebron0217 - Scientist (f/m) / PhD position
Project no:
Acebron0217

Project leader:

Project supervisor:
Acebrón, Sergio
Application deadline:
15. Sep 2017
Start of PhD project:
1. Oct 2017

Project description:

Title:
Regulation of Wnt signalling in adult stem cells and cancer
Summary:
The fate of adult stem cells is determined by the integration of different extracellular signals released from their niches. For example, Wnt ligands are essential for stem cell maintenance and tissue homeostasis across many organs. This PhD will focus on the analysis of the transduction of Wnt signals, notably in adult stem cells of the adrenal gland and the gut, as well as the investigation of how its misregulation leads to cancer in these organs.

The work will be conducted in novel mouse models for Wnt components, in stem cells and organoids cultured ex vivo, as well as in cancer-derived cell lines. You will learn how to work with these models to investigate a novel crosstalk between the Wnt signaling pathway and other cellular signals, and determine its relevance in stem cell renewal and malignant transformation.

As part of the PhD, you will edit novel endogenous effectors using CRISPR/Cas9, including in adult stem cells. You will analyse how mutations in these effectors impact the transduction and functions of Wnt ligands using specific reporters and markers in the above indicated models. You will also determine the molecular mechanisms underlying these processes by employing biochemical approaches established in our lab. You will use state-of-the-art microscopes, mouse techniques and ex vivo models to understand how Wnt signals are integrated in stem and cancer cells.

You can apply directly at the HBIGS portal or by email to Dr. Sergio Acebrón: sergio.acebron@cos.uni-heidelberg.de. Please include a motivation letter (+/- 500 words stating your scientific interests, aspects of your background, and previous research experience), contact details for 2 referees, and your CV.
References:
• Acebrón SP and Niehrs C. beta-catenin independent roles of Wnt/LRP6 signalling (2016) Trends Cell Biol, 26: 956-967

• Koch S, Acebrón SP, Herbst J, Hatiboglu G and Niehrs C. Post-transcriptional Wnt signaling governs epididymal sperm maturation (2015) CELL 163:1225-36

• Niehrs C and Acebrón SP. Mitotic and mitogenic Wnt signalling (2012) EMBO J 31: 2705-13.
Methods that will be used:
Mouse techniques, ex vivo culture of organoids, live and high-resolution imaging; Genome engineering; CRISPR; signal transduction studies, molecular and cellular biology.
Cooperation partners:
For this project, we collaborate with the group of Bon-Kyoung Koo at the IMBA (Vienna). In addition, our group forms part of a vivid and well-established network of groups in Heidelberg focusing on cell signalling.
Personal qualifications:
Applicants should hold a diploma/masters’ degree in life sciences with an excellent background in cell and molecular biology, and have strong laboratory, analytical and communication skills. Experience in mouse work is preferable but not required.
The candidate should be fluent in English, enthusiastic, motivated, self-driving and a critical thinker. The applicant should be able to work well in an international team environment.
Keywords:
Wnt signaling, mouse models, stem cells, CRISPR, imaging, cancer