Position: PhD Student in Wnt signaling
Department: Molecular Embryology
Code number: 2021-0077
The German Cancer Research 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.
Project I: 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. (Prof. Christof Niehrs).
Project II: Wnt signaling & protein kinase regulation
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 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 PhD student 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 phenomenological but at a mechanistic level. (Prof. Christof Niehrs).
Project III: Wnt signaling & protein kinase in embryonic development
Fundamental mechanisms of vertebrate cell and developmental biology were first discovered by studying the African clawed frog Xenopus laevis. The Nobel Prizes for Physiology or Medicine to Hans Spemann (1935), Tim Hunt (2001), and John Gurdon (2012) testify Xenopus as powerful model systems for biomedical research. During animal development, Wnt signaling plays an eminent role for the anterior-posterior patterning of the neural plate. By virtue of the utility of Xenopus, we have previously identified DDX3 as the key Wnt regulator in this context (Criciat et al SCIENCE 2013). We further found that other members of DDXs may also function as crucial kinase regulators in Wnt signaling.
The PhD project aims characterization of the novel DDX-protein kinase pair in Wnt signaling during Xenopus development by gain- and loss-of-function experiments. Thus, the project encompasses both developmental biology and molecular biology, including embryo microinjection, in situ hybridization, transplantation, in vitro culture as well as immunofluorescence, qPCR and CRISPR/CAS9 mediated gene editing. (Prof. Christof Niehrs)
Applicants should hold a master's degree in biology / life sciences with an excellent background in biochemistry, cell or molecular biology. Candidates should be self-motivated and be 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- & Masterzeugnis), a cover letter stating research and career interests and the expected availability date.
In addition to posting your application on our online application portal, please have two letters of recommendation sent directly to email@example.com by the authors.
Incomplete applications will not be considered or acknowledged.
- Interesting, versatile workplace
- International, attractive working environment
- Campus with modern state-of-the-art infrastructure
- Access to international research networks
- Doctoral student payment including social benefits
- Flexible working hours
- Comprehensive training and mentoring program through the Helmholtz International Graduate School
Earliest Possible Start Date: 01.06.2021
Duration: The position is limited to 3 years.
Application Deadline: 27.04.2021
Phone +49 6221/42-4693
Please note that we do not accept applications submitted via email.