German Cancer Research Center in the Helmholtz Association (DKFZ)

Postdoc in Wnt signalling

German Cancer Research Center in the Helmholtz Association (DKFZ)

Heidelberg, Germany

The German Cancer Re search Center is the largest biomedical research institution in Germany. With more than 3,000 employees, we operate an extensive scientific program in
the field of cancer research.

The Division of Molecular Embryology is seeking a
Postdoc in Wnt signalling
(Ref-No. 2019-0375)

Description:
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. 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 kinaseactivation 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.

Your profile:
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.

The position is limited to 2 years with the possibility of prolongation.
The position can in principle part-time.

For further information please contact
Nadine Steinhübel, phone +49 6221 42-4693.

The German Cancer Research Center is committed to increase the percentage of female scientists and encourages female applicants to apply. Among candidates of equal aptitude and qualifications, a person with disabilities will be given preference.

To apply for a position please use our online application portal (www.dkfz.org).

We ask for your understanding that we cannot return application documents that are sent to us by post(Deutsches Krebsforschungs zentrum, Personalabteilung, Im Neuen heimer Feld 280, 69120 Heidelberg) and that we do not accept applications submitted via email. We apologize for any inconvenience this may cause.

Please apply via recruiter’s website.

Quote Reference: 2019-0375

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