S.T. Raterman MSc (Sophie)

PhD project: The molecular etiology of craniofacial malformations using zebrafish models.
About 1 in 500 children are born with a cleft lip or palate (CLP) (in Dutch: schisis). CLP occurs in isolated form or as part of a syndrome. Although advanced surgical options are available to repair clefts after birth, affected individuals still experience lifelong consequences. These can include hearing complications, speech impairments and psychological problems.
Many genetic risk factors of isolated CLP have been identified using patient data. In parallel, environmental factors are found to contribute to CLP etiology; smoking, alcohol use and taking anti-epileptic medicine during pregnancy can increase the chances of cleft lip and palate in babies. Although many causative factors are known, for most, the molecular etiology is not well-characterized. Interactions between genes and environment further complicate mechanistic investigations into disease etiology.
Zebrafish are a versatile vertebrate disease model that comprises many advantages for the study of congenital defects; transparency during embryo and larval stages, high progeny and a well annotated gene homology to humans. Zebrafish can be used as a model for CLP as craniofacial development is similar between vertebrate species; the zebrafish skull contains the ethmoid plate which can be compared to the human hard palate. We take advantage of these similarities to study CLP etiology for genetic and environmental factors causes. We use CRISPR/Cas9 to generate zebrafish mutants for genes involved in CLP in humans, and study mutant craniofacial development. In parallel we investigate the interactions of environmental factors on craniofacial development.