德国癌症研究中心博士后职位

　　职位描述：

　　德国癌症研究中心是德国最大的生物医学研究机构。我们拥有约3,000名员工，在癌症研究领域开展了广泛的科学计划。分子胚胎学部正在寻求一个Wnt信号传输中的博士后（参考编号2019-0028）

　　描述：

　　项目I：在发育，干细胞和癌症中的Wnt信号传导和相分离

　　在过去几年中，相关分离成无膜细胞器通常已经获得了显着的兴趣，并且它发生在细胞核与质膜之间的许多细胞环境中。我们发现Wnt信号通过涉及动态液滴和无序蛋白结构域的液相分离介导的证据。在这个项目中，我们的目标是进一步表征这一现象：如何诱导和调节相分离？这个过程中关键的分子参与者是什么？相分离对Wnt信号传导有什么影响？您将采用这一新兴领域中使用的尖端技术，包括活细胞的共聚焦荧光显微镜，光漂白，超分辨率和单分子显微镜，微流体，生物信息学，CRISPR-Cas9基因编辑，蛋白质表达和体外聚集试验。 （Christof Niehrs教授）

　　项目II：Wnt信号传导，激酶酶学和癌症药物开发

　　Wnt信号传导是细胞分化和肿瘤发生的关键过程。蛋白激酶尤其在Wnt信号传导中起着重要作用。在蛋白激酶中，酪蛋白激酶1（CK1）家族在多个水平上调节Wnt信号传导途径。在此背景下，我们先前已将DEAD-box RNA解旋酶DDX3鉴定为胚胎发育中Wnt-β-连环蛋白网络的调节剂，其中它充当CK1的变构激活剂（Cruciat等人，2013）。此外，DDX3和CK1都是致癌基因，因此他们的研究与新型癌症治疗的发展有关。值得注意的是，DDX3是Wnt介导的成神经管细胞瘤中的关键易感基因，因此了解其作用机制是开发针对该信号传导模块的抗癌药物的先决条件。

　　该博士项目的目的是通过阐明CK1-DDX3蛋白复合物的酶学来揭示变构激酶活化的分子基础。因此，该项目涉及CK1-DDX3蛋白复合物的生产，纯化和酶动力学以及不同DDX解旋酶，底物，ATP，RNA和抑制剂的影响。因此，博士后将接触各种方法并接受可靠的生化培训，这将构成他/她理解生理过程的能力的基础，不仅是现象学的，而且是机械的。 （Christof Niehrs教授）。

　　申请人资料：

　　申请人应持有生物学/生命科学博士学位，具有生物化学，细胞或分子生物学方面的优秀背景。候选人应该是自我激励的，能够独立地进行研究项目以及合作。良好的书面和口头英语能力至关重要。

　　申请应包括简历（德国人：Abitur-和Diplomzeugnis的副本），说明研究和职业兴趣的求职信，证书，预期可用日期，完整的出版物清单和2-3个参考文献。

　　不完整的申请将不予考虑或承认。

　　该职位限于2年，有可能延长。

　　该职位原则上可以是兼职。

　　欲了解更多信息，请联系Monika Bock，电话：+49 6221 421420。

　　德国癌症研究中心致力于提高女科学家的比例，并鼓励女性申请者申请。在具有相同资质和资格的候选人中，将优先考虑残疾人。

　　要申请职位，请使用我们的在线申请门户网站（www.dkfz.de）。

　　我们要求您理解我们无法退回通过邮寄发送给我们的申请文件（Deutsches Krebsforschungszentrum，Personalabteilung，Im Neuenheimer Feld 280,69120 Heidelberg），并且我们不接受通过电子邮件提交的申请。对由此造成的任何不便，我们深表歉意。

　　英文原文：

　　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.

　　The Division of Molecular Embryology is seeking a

　　Postdoc in Wnt signaling

　　(Ref-No. 2019-0028)

　　Description:

　　Project I: Wnt signaling and phase separation in development, stem cells and 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)

　　OR

　　Project II: Wnt signaling, kinase enzymology and 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 PhD 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 phenomenological but at a mechanistic level. (Prof. Christof Niehrs).

　　Your profile:

　　Applicants should hold a PhD 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 in written and oral English is essential.

　　Applications should include a CV (Germans: copies of Abitur- and 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 priciple be part-time.

　　For further information please contact Monika Bock, phone +49 6221 421420.

　　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.de).

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