Position: Postdoc in Wnt signalling
Department: Molecular Embryology
Code number: 2019-0375
The German Cancer Research Center is the largest biomedical research institution in Germany. With approximately 3,000 employees, we operate an extensive scientific program in the field of cancer research.
Wnt signaling & phase separation in development, stem cells & cancer
Phase-separation into membrane-less organelles in general has gained significantly in interest over the past years, and it occurs in many cellular contexts between the cell nucleus to the plasma membrane. We found evidence that Wnt signaling is mediated by liquid phase separation involving dynamic liquid droplets and disordered protein domains. In this project, we aim to characterize this phenomenon further: How is phase separation induced and regulated? What are the key molecular players in the process? What are the consequences of phase separation for Wnt signaling? You will employ cutting-edge techniques used in this emerging field, including confocal fluorescence microscopy of live cells, photo-bleaching, superresolution and single-molecule microscopy, microfluidics, bioinformatics, gene-editing by CRISPR-Cas9, protein expression and in vitro aggregation assays.
Wnt signaling, kinase enzymology & cancer drug development
Wnt signaling is a key process in cell differentiation and oncogenesis. Protein kinases in particular play an eminent role in Wnt signaling. Among protein kinases, the casein kinase 1 (CK1) family regulates Wnt signaling pathway at multiple levels. In this context, we have previously identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt-β-catenin network in embryonic development, where it acts as an allosteric activator of CK1 (Cruciat et al SCIENCE 2013). Moreover, both DDX3 and CK1 are oncogenes and hence their investigation is of relevance for the development of novel cancer therapeutics. Notably, DDX3 is a key susceptibility gene in Wnt-mediated medulloblastoma and hence understanding its mechanism of action is a prerequisite to develop anti-cancer drugs targeting this signaling module.
The aim of this postdoc project is to unravel the molecular basis of the allosteric kinase-activation by elucidating the enzymology of the CK1-DDX3 protein complex. Thus, the project involves the production, purification and enzyme kinetics of the CK1-DDX3 protein complex and the influence of different DDX helicases, substrates, ATP, RNA and inhibitors. The postdoc will therefore be exposed to a variety of approaches and receive solid biochemical training, which will form the basis of his/her ability to understand physiological processes not only phenomenologically but at a mechanistic level.
Applicants should hold a PhD degree in biology/life sciences with an excellent background in biochemistry, cell or molecular biology. Experience with Wnt signaling is a plus. Candidates should be self-motivated and able to pursue research projects independently as well as in collaborations. A good command of written and oral English is essential.
Applications should consist of a single pdf file including a CV (Germans: copies of Abitur- & Diplomzeugnis), a cover letter stating research and career interests, certificates, expected availability date, a complete list of publications and 2-3 references.
Incomplete applications will not be considered or acknowledged.
- Interesting, versatile workplace
- International, attractive working environment
- Campus with modern state-of-the-art infrastructure
- Salary according to TV-L including social benefits
- Possibility to work part-time
- Flexible working hours
- Comprehensive further training program
- Access to the DKFZ International Postdoc Program
Earliest possible start date: 01.06.2020
Duration: The position is limited to 2 years with the possibility of prolongation.
The position can in principle part-time.
Application deadline: 19.12.2019
Phone +49 6221/42-4693
Please note that we do not accept applications submitted via email.