Characterization and Structure Determination of Novel Protein Kinase Regulators involved in Cancer

Cell signaling is a key process in cell differentiation and oncogenesis. Protein kinases in particular play an eminent role in development, stem cells and cancer. 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.

The aim of this PhD project is to unravel the molecular mechanisms of the allosteric kinase-activation by an interdisciplinary approach including structure determination of the CK1-DDX3 complex. Thus, the project involves the production, purification, and structure determination by X-ray crystallography. This project is pursued in close collaboration between Prof. Dr. Irmgard Sinning and Prof. Dr. Christof Niehrs. The student will predominantly work in the lab of Prof. Sinning and will be exposed to/trained in a variety of approaches central to structural biochemistry and molecular cell biology.

Techniques employed include:
Standard molecular biology methods, DNA transfection, protein expression in different cell types, Western blot analysis, luciferase reporter assays, protein kinase assays, high-end protein purification techniques, protein crystallization, advanced X-Ray structure determination using synchrotron radiation sources, HDX-MS, thermophoresis, ITC, UV and CD spectroscopy.

Desired qualifications:
Experience in biochemistry, cell- or molecular biology

Starting Date: any time 2017
Duration: 3 years, extendable

Note: Please send applications including letter of motivation, full CV and exam results (including Abitur if applicable) IN A SINGLE PDF FILE. Only applications send IN A SINGLE PDF FILE will be considered.

About DKFZ Heidelberg:To perform research into cancer is the task of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) according to its statutes. DKFZ is the largest biomedical research institute in Germany and a member of the Helmholtz Association of National Research Centers. In over 90 divisions and research groups, our more than 3,000 employees, of which more than 1,200 are scientists, are investigating the mechanisms of cancer, are identifying cancer risk factors and are trying to find strategies to prevent people from getting cancer.They are developing novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful.