PhD Position: Druggable pathways in EMT-like transition of Ewing sarcoma
Molecular Biology of Solid Tumors
"VAGABOND Validation of Actionable Genomic ABerrations in a paediatric Oncology Network for Doctorate students" aims to create a multidisciplinary and multi-sectoral program to validate new therapeutic interventions in paediatric cancer. The program is funded by the European Commission under the Horizon 2020 programme (Marie Sklodowska-Curie Actions Innovative Training Network) and offers 15 fully funded PhD positions. The consortium is coordinated by the Princess Máxima Center for Pediatric Oncology and consists of 12 academic and 6 non-academic partners from 8 European countries.
The research projects are focused on genetic, epigenetic and immunological targets. The PhD position at the CCRI is focused on druggable pathways in EMT-like transition of Ewing sarcoma.
Find more information on VAGABOND here.
Objectives of the Project
Identifying and targeting of key molecular determinants of migratory and invasive capacity in Ewing sarcoma. Fluctuations in the driver oncogene EWS-FLI1 have previously been reported to initiate epithelial-to-mesenchymal-transition (EMT)-like phenotypic changes in Ewing sarcoma through activation of YAP/TAZ/TEAD signalling. Accordingly, blocking YAP/TAZ/TEAD complex formation by a small molecule inhibitor (verteporfin) reduced tumour cell migration and the metastatic potential of Ewing sarcoma in a mouse model. We will mimic EWS-FLI1 fluctuation in two genetically modified Ewing sarcoma cell lines with small molecule-inducible EWS-FLI1 degradation and quantify migratory and invasive capacity of tumour cells using Boyden chamber assays. We will perform a pooled CRISPR/Cas9 drop-out screen to identify molecular dependencies of Ewing sarcoma EMT-like transitions using migratory and invasive capacity as read-out. In addition, we will screen a compound library of 309 unique drugs (CLOUD) including verteporfin for single and pairwise combinatorial activity on tumour cell migration. Novel targets and compound combinations will be validated in PDX-derived Ewing sarcoma cells using a novel 3D bio printed scaffold model recently established in the lab, and in a Ewing sarcoma xenograft model in zebrafish larvae.
We expect to identify molecular key players of the early steps of Ewing sarcoma metastasis, and to propose novel therapeutic drug combinations
We offer a challenging position in a meaningful, inspiring and international setting with an outstanding working atmosphere in a strong team. Flexible working hours, discounted lunch in our canteen and other great benefits as well as our excellent location in the center of Vienna with great public transport connections complete the position. We offer a fair and attractive salary package according to the FWF salary scheme (https://www.fwf.ac.at/en/research-funding/personnel-costs/) for this PhD position.
Who we are
The St. Anna Children’s Cancer Research Institute (CCRI), located in the center of Vienna, the world’s most livable city and one of Europe’s most important places for biomedical research and life sciences, is an international and multidisciplinary competence center striving to improve treatment of children and adolescents with cancer by connecting translational and clinical research with open-minded exploration of basic disease mechanisms. Through close cooperation between clinic and research, the CCRI provides an ideal environment for cutting-edge research and its translation into clinical practice. To achieve our ultimate goal of advancing the well-being of patients, the CCRI constantly pushes scientific boundaries and strongly promotes close collaboration and exchange with external institutions like the Medical University of Vienna, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) and the Institute of Molecular Pathology (IMP).
The CCRI is an equal opportunity employer. We value diversity and are committed to providing a work environment of mutual respect to everyone without regard to race, color, religion, national origin, age, gender identity or expression, disability, or any other characteristic protected by applicable laws, regulations and ordinances.
Please upload your application documents via the online platform of VAGABOND here.