職位描述：

　　德國癌癥研究中心是德國最大的生物醫(yī)學研究機構。我們擁有約3,000名員工，在癌癥研究領域開展了廣泛的科學計劃。分子胚胎學部正在尋求一個Wnt信號傳輸中的博士后（參考編號2019-0028）

　　描述：

　　項目I：在發(fā)育，干細胞和癌癥中的Wnt信號傳導和相分離

　　在過去幾年中，相關分離成無膜細胞器通常已經獲得了顯著的興趣，并且它發(fā)生在細胞核與質膜之間的許多細胞環(huán)境中。我們發(fā)現(xiàn)Wnt信號通過涉及動態(tài)液滴和無序蛋白結構域的液相分離介導的證據(jù)。在這個項目中，我們的目標是進一步表征這一現(xiàn)象：如何誘導和調節(jié)相分離？這個過程中關鍵的分子參與者是什么？相分離對Wnt信號傳導有什么影響？您將采用這一新興領域中使用的尖端技術，包括活細胞的共聚焦熒光顯微鏡，光漂白，超分辨率和單分子顯微鏡，微流體，生物信息學，CRISPR-Cas9基因編輯，蛋白質表達和體外聚集試驗。 （Christof Niehrs教授）

　　項目II：Wnt信號傳導，激酶酶學和癌癥藥物開發(fā)

　　Wnt信號傳導是細胞分化和腫瘤發(fā)生的關鍵過程。蛋白激酶尤其在Wnt信號傳導中起著重要作用。在蛋白激酶中，酪蛋白激酶1（CK1）家族在多個水平上調節(jié)Wnt信號傳導途徑。在此背景下，我們先前已將DEAD-box RNA解旋酶DDX3鑒定為胚胎發(fā)育中Wnt-β-連環(huán)蛋白網絡的調節(jié)劑，其中它充當CK1的變構激活劑（Cruciat等人，2013）。此外，DDX3和CK1都是致癌基因，因此他們的研究與新型癌癥治療的發(fā)展有關。值得注意的是，DDX3是Wnt介導的成神經管細胞瘤中的關鍵易感基因，因此了解其作用機制是開發(fā)針對該信號傳導模塊的抗癌藥物的先決條件。

　　該博士項目的目的是通過闡明CK1-DDX3蛋白復合物的酶學來揭示變構激酶活化的分子基礎。因此，該項目涉及CK1-DDX3蛋白復合物的生產，純化和酶動力學以及不同DDX解旋酶，底物，ATP，RNA和抑制劑的影響。因此，博士后將接觸各種方法并接受可靠的生化培訓，這將構成他/她理解生理過程的能力的基礎，不僅是現(xiàn)象學的，而且是機械的。 （Christof Niehrs教授）。

　　申請人資料：

　　申請人應持有生物學/生命科學博士學位，具有生物化學，細胞或分子生物學方面的優(yōu)秀背景。候選人應該是自我激勵的，能夠獨立地進行研究項目以及合作。良好的書面和口頭英語能力至關重要。

　　申請應包括簡歷（德國人：Abitur-和Diplomzeugnis的副本），說明研究和職業(yè)興趣的求職信，證書，預期可用日期，完整的出版物清單和2-3個參考文獻。

　　不完整的申請將不予考慮或承認。

　　該職位限于2年，有可能延長。

　　該職位原則上可以是兼職。

　　欲了解更多信息，請聯(lián)系Monika Bock，電話：+49 6221 421420。

　　德國癌癥研究中心致力于提高女科學家的比例，并鼓勵女性申請者申請。在具有相同資質和資格的候選人中，將優(yōu)先考慮殘疾人。

　　要申請職位，請使用我們的在線申請門戶網站（www.dkfz.de）。

　　我們要求您理解我們無法退回通過郵寄發(fā)送給我們的申請文件（Deutsches Krebsforschungszentrum，Personalabteilung，Im Neuenheimer Feld 280,69120 Heidelberg），并且我們不接受通過電子郵件提交的申請。對由此造成的任何不便，我們深表歉意。

　　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.

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