Gene mutations or environmental factors such as infection or drugs can have genome-wide effects on gene expression levels across many different pathways. However, it is not always clear which of these perturbations can be buffered by the system and which lead to detrimental outcomes as reflected in morphological changes or reduced health. Our research focusses on investigating in vivo gene regulatory responses to challenges such as genetic mutations, chromatin disruption and infection. Specifically, we use our zebrafish mutant archive of ~43,000 alleles covering 60% of protein-coding genes, CRISPR/Cas9 mutagenesis and genome-wide sequencing approaches to understand the relationship of chromatin structure, transcriptional changes and phenotypic outcomes. For example, partial loss of gene function can have substantial effects on genome-wide gene expression levels without gross morphological defects. This provides an opportunity to dissect gene regulatory networks and distinguish network-specific, but tolerated gene expression changes from those that affect organismal development and health.
Dooley CM, Wali N … Busch-Nentwich EM; The gene regulatory basis of genetic compensation during neural crest induction. bioRxiv 2018. doi.org/10.1101/314534
Perez-Garcia V … Busch-Nentwich EM … Hemberger M; defects are highly prevalent in embryonic lethal mouse mutants. Nature 2018. doi: 10.1038/nature26002
White RJ, Collins JE … Busch-Nentwich; A high-resolution mRNA expression time course of embryonic development in zebrafish. Elife 2017. DOI: 10.7554/eLife.30860
Scahill CM, Digby Z … Busch-Nentwich;The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish. Wellcome Open Research 2017. DOI: 10.12688/wellcomeopenres.12530.2
Scahill CM, Digby Z … Busch-Nentwich;Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish. PLoS Genetics 2017. DOI: 10.1371/journal.pgen.1006959