Postdoctoral Research Fellow in Bioinformatics – Systems Biology of Childhood Cancer
Description
We are looking for an enthusiastic bioinformatician who would like to pursue her/his post-doctoral research in the field of pediatric solid tumors. You will work in a multidisciplinary environment in the group of the scientific director Heinrich Kovar on the biology of Ewing sarcoma. Our lab is based at the Children's Cancer Research Institute (CCRI) of the St. Anna Kinderkrebsforschung Association in Vienna (Austria). The Institute is located in the heart of beautiful Vienna, a European metropolis full of history, music and fine arts. Vienna has been voted “most livable” city in the world for the 4th year in a row. CCRI is a renowned research institution with tight links to the St. Anna Children's Hospital, a leading pediatric cancer center in Europe. The ultimate aim of CCRI research is to improve treatment outcome of malignant diseases in children and adolescents by performing basic, translational and clinical research. Our comprehensive cancer center entertains close collaborations with many other research and clinical institutions worldwide. Additional information on the CCRI can be found at http://science.ccri.at/.
The lab
Our group has been studying the molecular underpinnings of Ewing sarcoma for many years. We try to understand, how a single genetic aberration, the EWS-FLI1 gene fusion, can drive the pathogenesis of this disease. Since recent genome sequencing studies confirmed an extremely low number of mutations and the absence of recurrent aberrations other than the EWS-ETS gene rearrangement and facultative whole chromosome copy number changes, it is plausible that if activated in the right developmental, epigenomic and genomic context, EWS-FLI1 is sufficient to induce and maintain malignancy. We want to learn how EWS-FLI1 uncouples normal developmental and microenvironmental signalling cues to lead to self-sufficiency, unrestricted growth and differentiation arrest. To this end, we have taken a systems approach to the study of perturbed gene regulatory networks. We are working with large scale data sets including RNA-seq, ChIP-seq, PAR-clip, whole genome bisulfite sequencing, exome sequencing and mass spectrometry. We use both in vivo and in vitro models and we have access to relevant clinical material.
Our goal is to define the epigenomic, genomic and proteomic context that offers a permissive environment for EWS-FLI1 induced malignancies.
Most recent relevant publications:
Schwentner R, et al. EWS-FLI1 employs an E2F switch to drive target gene expression. Nucleic Acids Res. 43(5):2780-9. PMID:25712098
Tomazou-EM, et al. (2015). Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Reports, 10:1-14. PMID:25704812
Ban J, et al. (2014). Suppression of deacetylase SIRT1 mediates tumor-suppressive NOTCH response and offers a novel treatment option in metastatic Ewing sarcoma. Cancer Res. 15,74:6578-88. PMID:25281719
Niedan S, et al. (2013). Suppression of FOXO1 is responsible for a growth regulatory repressive transcriptional sub-signature of EWS-FLI1 in Ewing sarcoma. Oncogene 33(30):3927-38. PMID:23995784
Bilke S*, Schwentner R*, et al. (2013). Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome Res. 11:1797-1809. PMID:23940108
The Project
Developing and applying computational algorithms in a systems biology manner to dissect aberrant transcriptional regulation by the EWS-FLI1 oncogene. Potential topics to work on include: Ewing sarcoma epigenetics; role of non-coding RNAs in Ewing sarcoma; transcription factor networks. The candidate will have access to high through-put data generated from our EU-funded projects. A competitive postdoc salary will be paid that largely orientates along the guidelines of the Austrian Science Fund (http://www.fwf.ac.at/fileadmin/files/Dokumente/Personalkostensaetze/personnel-costs-2014.pdf). The position is immediately available for three years. A success dependent contract extension beyond this period is possible.
The Candidate
An ideal candidate should hold a Ph.D. degree in life sciences, computational biology, computer science, mathematics or related fields, with excellent programing skills. Experience in next-generation sequencing data analyses (as evidenced by publications in peer-viewed journals) and with R/Bioconductor is a significant plus. Must have excellent organizational and communication skills, and the ability to develop new project ideas. The ability and will to write papers and grant applications is warranted. Enthusiasm, self-motivation, creativity and proactive approach to solving problems are highly desirable. Applicants should not have more than 5 years of post-doctoral experience.
Applications
Please submit motivation letter, curriculum vitae, academic transcripts and contact details of three referees to
Heinrich Kovar (heinrich.kovar@ccri.at)
