Dimitris Beis is head of the zebrafish models of Human Disease laboratory in BRFAA. Zebrafish are increasingly used worldwide as model organisms in biomedical research for answering fundamental and applied problems in biological and health-related fields. A unique set of properties (numerous offspring, optical transparency of embryos, amenability to genetic and chemical screens) has made them powerful vertebrate research models.
The long-term goal of my research is to elucidate how cardiac valves form and function to support appropriate heart performance throughout the life of vertebrates. The heart is one of the first organs to form and function during vertebrate development before its morphogenesis is completed. Cardiac valves derive from endocardial cells and form along the antero posterior axis of the vertebrate heart to prevent retrograde blood flow. Valve morphogenesis happens while the heart is contracting and blood flows through the endocardium. The central question that arises is how morphogenetic changes and changes in function during heart development are integrated. Defects in valvulogenesis affect 1% of the population and cause impaired heart function with lifelong complications.
In higher vertebrates, developmental abnormalities of the heart often lead to early lethality making it difficult to study later aspects of heart development such as valve formation in vivo. We have analyzed the cellular architecture of the zebrafish heart during AV valve development and isolated a number of mutations with defects in different steps of valvulogenesis (Beis et al., 2005), showing that even a complex morphogenetic process such as cardiac valve development could be broken down into genetically distinct steps. We are currently using positional cloning to isolate the mutated genes and high-resolution microscopy to analyze their phenotypes.
Zebrafish embryos develop externally; they are transparent allowing for non-invasive observation and survive even in the total absence of circulation until very late stages of development. All of these characteristics, together with the ease to do forward and reverse genetics, make zebrafish an ideal system to develop Disease Models and conduct chemical genetic and small molecule screens.