- Cancer Research
- Ludwig Boltzmann Institute for Cancer Research
- Closing Date
Blood cancer metabolism control through the STAT5 transcription factor and JAK2 kinase
The JAK2-STAT5 core cancer signaling pathway gained increased attention due to frequent hyperactivation. STAT5 activation and tyrosine phosphorylation is mainly triggered by JAK tyrosine kinases, themselves frequently mutated and hyper-activated in cancer. We published in 2017 (Freund et al., Leukemia, 2017) on a new post-translational modification, namely O-GlcNAc glycosylation of STAT5 at threonine 92 to be essential for transformation identifying a metabolic sensor linking cancer cell growth to metabolism (http://lbicr.lbg.ac.at/en/metabolism-drives-growth-and-division-cancer-cells). We used a hyperactive gain-of-function variant of STAT5 lacking O-GlcNAc and now we address the upstream JAK2 kinase for similar modification. We have established tools for STAT5 and for JAK2 to study the changes in O-GlcNAcylation under variable nutritional status being either high or low in glucose or glutamine. Within the MSc thesis we want to analyze O-GlcNAc-modified JAK2 in human cancer cells and map its O-GlcNAc modification by mutagenic analysis. We will generate an O-GlcNAc-deficient hyperactive JAK2V617F variant. Furthermore, we will reconstitute STAT5- or JAK2-deficient mouse embryonic fibroblasts with specific STAT5- or JAK2-O-GlcNAc-deficient variants to gain insight into transcriptional target gene regulation using gene expression profiling with RNA-Seq and bioinformatics analysis. Moreover, ChIP-Seq is planned for essential histone modifications and STAT5.
Freund et al. O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies. Leukemia; doi: 10.1038/leu.2017.4
We are looking for a talented and highly motivated MSc student with interest in cancer research with the following skills.
- Knowledge in biology
- Accuracy and reliability
- Interpersonal skills and ability to work in an international team
- Written and oral communication skills in English
- Experience with cell culture, biochemical and molecular biology methods
The MSc student will gain experience in cell culture techniques, FACS, cloning, transfection, PCR, qPCR, Western blotting, IP, RNA-Seq, bioinformatics analysis basics and ChIP-Seq protocols. Participation in group meetings and progress reports of the institute will encourage scientific communication skills.
Duration: 10-12months incl. written Master thesis with the possibility of extension
Compensation: 440 €/month
Place of work: Veterinärplatz 1; 1210 Vienna; Austria
Start: as soon as possible
Application: Please send per email your cover letter, detailed Curriculum Vitae and arrange for at least one letter of recommendation
- Main contact
- Name: Patricia Freund