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Project

BRIP1 controlling replicative stress in the neuroblastoma tumor genome: functional exploration and zebrafish modelling

Neuroblastoma is a tumor arising in the nervous system and almost exclusively exist in children younger than five. Unfortunately, half of these tumors are very aggressive and still extremely difficult to cure. In recent decades it has been shown that neuroblastoma tumors almost have no mutations, but instead a lot of copy number alterations occur. One of these copy numbers is gain of 17q which is correlated with poor patient outcome. In this research project, I will make use of zebrafish to further unravel the role of 17q gain in neuroblastoma. In a first step, I will investigate if BRIP1 functions to control replication stress in neuroblastoma tumors. This will be studied both in vitro (in neuroblastoma cell lines) and in vivo (in zebrafish). Using the dTAG technology a new transgenic BRIP1 zebrafish model will be created where BRIP1 can be quickly degraded upon addition of dTAG13. This will help me to further understand if BRIP1 is important in the initiation of the tumor development or in maintaining the tumor genome. In a second step, I will use zebrafish to identify which domains in BRIP1 are important for neuroblastoma development. Several mosaic injections will be performed, were each construct will have a defect in a different domain. In a final step, potential new interesting domains in BRIP1 will be identified using a tilling drop-out screen.

Date:1 Nov 2020 →  Today
Keywords:Generation of transgenic zebrafish models for neuroblastoma, CRISPR-CAS, Structure function analysis, Cancer Biology
Disciplines:Cancer biology, Genetics, Transcription and translation