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PhD position in Molecular Biology - Functional characterisation of transcriptional targets of TOP2A poisoning in cancer models

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In the field of  “Functional characterisation of transcriptional targets of TOP2A poisoning in cancer models” the research group of Prof. Leszek Wojnowski offers one PhD project.

Most classic anticancer drugs are toxic towards non-cancerous cells due to the interference with the fundamental cellular processes of DNA metabolism and mitosis. They are gradually being replaced by drugs targeting molecules and processes more specific to cancer cells, a development largely driven by advances in tumor biology and rational drug design. For example, the identification of the bcr-abl fusion protein, exclusive to chronic monomyelocytic leukemia, led to the development of the well-tolerated tyrosine-kinase inhibitor imatinib. The alternative approach of finding specific effectors of cytotoxic drugs has not been explored, as the existence of such effectors seems less likely. On the other hand, cytotoxic drugs lead to remarkably specific gene expression signatures and they also exhibit a degree of cancer specificity. 

Poisoning of topoisomerase II alpha (TOP2A) by anthracyclines or epipodophyllotoxins is the cornerstone of many anti-cancer therapies. The cytotoxic effect is attributed to the accumulation of permanent DNA double-stranded breaks (DSB) resulting in apoptosis. Our observations indicate that the cytotoxicity is contributed to by expression changes of specific genes implicated e.g. in DNA repair. The aim of this project is to characterize the potential of these genes as targets for the development of more specific and therefore less toxic drugs mimicking TOP2A poisons. To this end, the expression of these genes will be manipulated by genome editing and RNAi interference in cellular and animal models of cancer. The effects will be investigated in the context of “hallmarks of cancer”. We also want to explore if the transcriptional repression of these genes may be responsible for the poorly understood radio-sensitization conferred to cancer cells by TOP2A poisons. Altogether the project is expected to explore specific, TOP2A-mediated transcriptional programs to selectively target cancer cells.   

We offer
•    The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
•    A stimulating, diverse and international research environment
•    Advanced training opportunities
•    A competitive stipend

Required qualifications
•    Master or Diploma
•    Motivation to solve complex biological problems
•    Excellent communication skills

Starting date: October 2015 or later
Duration of stipend: 3 years, with the possibility of extension
Deadline for registration (exclusively online via web form):  20 June 2015


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Details der Stellenanzeige

Befristete Anstellung
Berufserfahrung nicht vorausgesetzt
Deutschland (Rheinland-Pfalz)
55128 Mainz
Biologie & Life Sciences, Pharma