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Description of the project: Anti-cancer treatments that combine multiple drugs at very low doses are emerging as a promising strategy. Recently, we have shown that a combination of 4 drugs targeting the MAPK signaling network is surprisingly effective in a lung and various other cancer cell line models. In contrast to traditional high dose single drug treatment strategies, cells do not acquire resistance to this treatment. However, we do not currently understand why this drug combination is so effective.
In this project, we will combine “snapshot” quantifications of many proteins simultaneously with live cell imaging data to systematically quantify the response of key signaling proteins to various single and multi-drug perturbations. We aim to elucidate how these affect the signaling network of these cells, the role that cell-to-cell variability plays, and how this relates to cell death or the emergence of drug resistance.
Function description: Your role will be to develop and apply computational approaches to analyze the data generated in the project and build computational models of the signaling networks. You will use these models to understand how the targeted signaling pathways behave under the various perturbations and how this determines the response of the cells to treatment and become resistant to anti-cancer drugs. You will formulate testable hypotheses that will be validated experimentally Finally, you will contribute to designing more effective drug combinations.
Research groups: This project will be jointly supervised by prof. Lodewyk Wessels, who heads the Computational Cancer Biology group at the Netherlands Cancer Institute (ccb.nki.nl), and dr. Evert Bosdriesz (www.evertbosdriesz.org), assistant professor in the Integrative Bioinformatics group at the Vrije Universiteit Amsterdam. The successful candidate will be employed at the NKI and will spend at least two days per week at the VU. The project is in close collaboration with the research groups of prof. René Bernards at the Netherlands Cancer Institute (https://www.nki.nl/research/research-groups/rene-bernards/) and prof. Hugo Snippert (https://hugosnippert.nl/) at the Hubrecht institute, and there will be ample opportunity to interact with these groups.
We are seeking a highly motivated PhD candidate with:
Fixed-term contract: 4 years.
Your temporary employment will be for a period of 4 years. The gross salary per month for our PhD will range from € 3.043,- to a maximum of € 3.695,- according to the standard PhD scales. The terms of employment will be in accordance with the Collective Labor Agreement for Hospitals. In addition you will receive a fixed end-of-year bonus (8,33%) and you will receive 8,33% holiday pay.
Your travel expenses will be reimbursed at € 0,19 per km. Free parking at the Antoni van Leeuwenhoek is also part of the package. Personnel is stimulated to use public transport and bicycle and therefore we offer an interesting arrangement for bikers and/or discount on the NS-business card.
For all secondary conditions visit: https://www.nki.nl/careers-study/how-to-apply/.
The Netherlands Cancer Institute
Plesmanlaan 121, 1066 CX, Amsterdam
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