Position: PhD position (Ref-No. 144/2008)
Description:
A hallmark of many tumours is their high glycolytic rate, strongly supporting Warburg’s dictum of a relationship between a glycolytic shift and malignant progression. This has a quite obvious selective advantage. Cells which shift to anaerobic glycolysis not only survive a hypoxic microenvironment, but are also resistant to acid-induced toxicity, caused by secretion of lactic acid during incomplete glucose metabolism. Since Human Papilloma Virus (HPV)-positive cells also depend on glycolysis for energy production, they are much stronger dependent on that pathway than normal cells. A glycolytic phenotype, which guarantees constant energy supply even when oxygen levels decreased, is apparently also an essential prerequisite to maintain transcriptional activity of the viral oncoproteins E6 and E7. In fact, this relationship seems to be an evolutionary well-designed circuit between sustained HPV transcription and oncoprotein functionality, since E7 itself is capable to reprogram the metabolism of its host cell. Accordingly, for a beneficial virus-host interaction it is reasonable that viral transcription, which continuously requires a high metabolic state for keeping up cell proliferation, is down-regulated by a negative feedback loop when the host cell is sensing low energy conditions. The general aim of this recently initiated project is to analyze the influence of nutrient depletion and metabolic stress on HPV-transcription and proliferation of cervical carcinoma versus non-malignant HPV-positive cells.
Reference: Nafz, J., De-Castro Arce, J., Fleig, V., Patzelt, A., Mazurek, S. and Rösl, F. (2007). Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB1. Biochemical Journal, 403: 501-510.
Job profile:
The highly motivated applicant should have a strong background in cell biology, molecular biology and biochemistry. Solid expertise in metabolic regulation and cell cycle control is required.
Applications should include a CV, publication(s), and addresses of two references.
For further information please contact Prof. Dr. Frank Rösl, phone +49 6221 42 4900.
The German Cancer Research Center is committed to increase the representation of women in science and encourages applications from qualified female scientists. Persons with disabilities will be given preference among equally qualified candidates.
Please your application to the following address:
Deutsches Krebsforschungszentrum
Personalabteilung
Im Neuenheimer Feld 280
D-69120 Heidelberg
September 18, 2008
or apply online: http://www.dkfz.de
