Postdoctoral researcher - Tumor development as a consequence of genomic instability and perturbed DNA replication
Your function within the department
The postdoc will join the research group of Hein te Riele, which is part of the division of Tumor Biology & Immunology. Research in the Te Riele group is focused on tumor development as a consequence of genomic instability and perturbed DNA replication.
Loss of G1/S control is a hallmark of cancer. However, unscheduled S-phase entry causes severe replication stress that through activation of the DNA damage checkpoint prohibits proliferation. How then do cancer cells deal with replication stress to maintain proliferative capacity? Can inhibition of pathways that cancer cells use to overcome the anti-proliferative effects of DNA replication stress be exploited to block propagation of human cancer?
We have addressed these questions in a model system of mouse embryonic fibroblasts devoid of the retinoblastoma (Rb) genes Rb1, Rbl1 and Rbl2 (pRB, p107 and p130 deficient). These G1/S-checkpoint-defective cells were capable of entering S-phase and synthesizing DNA in the absence of mitogenic stimuli, but suffered from severe replication stress causing cell cycle arrest. Remarkably, loss of Trp53 (p53) alleviated cell cycle arrest, but mitogen-independent proliferation appeared highly dependent on genes that minimize the deleterious consequences of replication stress.
In the present project, we wish to study whether these ‘replication rescue’ genes can serve as targets for therapeutic intervention. We will generate human cells with defects in the G1/S checkpoint and investigate whether and under which conditions these cells experience replication stress that makes them dependent on ‘replication rescue’ genes. We will study candidate genes but also perform CRISPR/Cas9 screens to identify novel genes that are critical for propagation of cells experiencing replication stress.
We seek an experienced and ambitious molecular/medical biologist at the postdoctoral level with an interest in fundamental research and its application in clinical practice. Besides a strong commitment to cancer research, extensive expertise in tissue culture and basic molecular biology techniques is essential.
Your career opportunities and terms of employment
You will join a dynamic international research division and collaborate with scientists and clinicians within and outside the NKI-AVL with expertise in different disciplines. You will have the opportunity to follow high-quality courses offered by the NKI postdoc career development program.
Your temporary employment is for a period of 2 years. The gross salary per month will be from € 3.421,- to € 3.840,- according to the FWG-function group 55, and depends on your previous experience. The terms of employment will be in accordance with the CAO Ziekenhuizen (Collective Labour Agreement for Hospitals) and can be consulted at http://www.nvz-ziekenhuizen.nl/cao-kenniscentrum/cao/download.
Amsterdam is a very lively city with many cultural amenities. The institute is located within a 20 minute tram or bicycle ride from the city center and within 20 minutes from Schiphol airport by car, bus or bicycle.
For further information about the position, please contact prof. dr. Hein te Riele, division of Tumor Biology & Immunology, tel. +31 20 512 2084 or firstname.lastname@example.org.
Your application letter and resume can be attached before December 10th, 2017 via the application button below.
After dispatch of the form you will receive a reaction as soon as possible.
Aquisition to this vacnacy is not appreciated.