The Princess Máxima Center for Pediatric Oncology is a new research hospital, which concentrates healthcare, research, and education with regard to cancer in children in a single location in the Netherlands. The institute aims to provide the highest level of care for all children with cancer and has the ambition to cure all children of cancer and to significantly reduce unwanted side effects. The center brings together the best possible care and scientific research, creating a unique interdisciplinary institute for pediatric oncology in Europe.
Molenaar Group
The research group of Jan Molenaar at the Princess Máxima Center is specialized in translational research in pediatric solid tumors with a focus on neuroblastoma. To this purpose, we have developed an experimental pipeline which starts with basic molecular biologic research and ends with implementation of new treatment options for pediatric cancer patients. Crucial in this pipeline is the use of high throughput analysis. We are running the compound screening facility in the Máxima, and we have initiated the iTHER precision medicine program for pediatric cancer.
Research project
In our group, we have identified frequent chromosomal rearrangement and genomic aberrations that are driving neuroblastoma and are therefore interesting drug targets. Although genomic amplification of Cyclin D1 and CDK4 occur in primary tumors and CDK6 shows significant overexpression in almost all neuroblastomas, inhibitors of these CDKs did not meet our expectations. As both genes were recently found to have non-canonical kinase‑independent functions, we expect that degradation of CDK4/6 proteins could largely increase the efficacy of the therapeutic intervention. In collaboration with the Dömling group from the Palacký University Olomouc, Czech Republic, we are developing new CDK degraders for neuroblastoma.
This PhD project aims at the pre-clinical evaluation of the degraders as new treatment options for neuroblastoma, by identifying the selective degradation of the CDK proteins. The in vitro testing of the degraders will be performed on a panel of neuroblastoma cell lines and neuroblastoma organoids. To determine the efficacy of the compounds, both the target-specific binding and target-specific protein degradation will be studied. The mode-of-action of the most successful degraders will be studied with RNA sequencing and Mass-spectrometry proteome analysis. Using the molecular characteristics of the cell lines and organoids, it can be determined if the compound efficacy in the cell lines and organoids is related to the target expression levels and genomic aberrations. Finally, the in vivo testing of the degraders will be performed using Neuroblastoma PDXs models.
Education And Skills
For the offered position, we are looking for a highly enthusiastic and motivated PhD candidate with a master’s degree in biomedical science, molecular/cellular biology, or equivalent. You have knowledge of several molecular skills and techniques, such as cell culture, western blot, co-immunoprecipitation, drug testing, and cell viability assays. Furthermore, experience and/or interest in data analysis using R or Python and animal experimentation is preferred. Furthermore, you like to collaborate and support other researchers and you are keen on clear communication with colleagues about research methods and results.
We offer
We offer a full-time position (36 hours) in an inspiring and multidisciplinary research environment. You will start on a temporary position for the duration of one year, with the intention to be extended for a total of four years. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.
Contact
We welcome you to contact Dr. M. van den Boogaard or Dr. J. Molenaar (click apply) for additional information about the vacancy.
Detailed information about the Princess Máxima Center for Pediatric Oncology can also be found at www.prinsesmaximacentrum.nl.
Apply for this position?
You can apply for this position until October 8th by pressing the apply button on this screen. Our preferred start date for this position is the 1st of January 2024.
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