Characterisation of the mechanism of HIF mediated genoprotection in zebrafish

Failing DNA-repair and the resulting genome instability is now recognized to be
a major factor in two important diseases that are becoming more and more
prevalent due to our aging population: cancer and neurodegeneration.
While studying the hypoxic signaling pathway in zebrafish we identified a
surprisingly strong effect of HIF activation on the protection of cells against DNA
damaging treatments. We found that embryos with a strongly activated HIF
pathway survived otherwise lethal doses of irradiation and it could even protect
embryos that have a mutation in certain DNA repair genes like BRCA2. These
data suggest that HIF can activate as yet unknown genoprotective mechanisms
This project aims to understand and exploit this genoprotective effect of HIF,
using zebrafish genetics, fluorescent protein transgenics and technologies
including CRISPR and CRISPRi, to identify and characterize the pathways
involved in HIF based protection against genotoxins.