WP2

Zebrafish Developmental Genomics Laboratory

Cecilia Lanny Winata, Head of Zebrafish Developmental Genomics Laboratory is a new group leader selected during an open international competition organised jointly with MPI-HLR in Bad Nauheim, our strategic partner for the creation and development of the FishMed Centre. The group located in IIMCB has full access to MPI-HLR equipment, animal facilities and genetic modification techniques for zebrafish and mice. The expertise of the new group leader and her staff  will further help us achieve a critical mass for the development of competitive and innovative zebrafish projects.

Zebrafish Developmental Genomics Laboratory is dedicated to the study of developmental processes by applying genomics methods in combination with experimental embryology, genetics, and biochemistry. The aim is to understand the complex transcriptional regulatory mechanism of embryonic development in vivo. Currently our research focuses on elucidating the downstream regulatory mechanism of heart development by cardiac transcription factors (TFs) and characterization of epigenetic profiles during heart development. A comprehensive understanding of the molecular regulatory networks governing heart development will be a crucial step to a better understanding of the mechanism of congenital heart diseases. The study of heart development poses a unique challenge due to the importance of the organ for survival. Disruption to factors regulating the early steps of heart formation, cause early embryonic lethality. The zebrafish (Danio rerio) alleviates this problem by allowing access to developing embryos right after fertilization and its ability to survive without a functioning heart up to a comparatively late stage of development. Taking advantage of this model organism, many genes regulating heart development have been identified. However, despite these advances, considerable challenges to understand the mechanism of heart development still exist. Firstly, there is still a lack of knowledge of molecular mechanism and downstream targets of cardiac TFs. Furthermore, the interconnectivity of their mechanisms and functions render it difficult, and possibly of little meaning, to make isolated assessments of individual factors in the characterization of a particular phenotypic outcome. Secondly, the transcription of genes are modulated by cis regulatory elements located in non-coding regions of the genome, which also serve as binding sites for TFs. Thus, mutations in these regulatory elements equally affect developmental outcome as mutations in coding regions. However, there is still a lack of systematic resource for these elements and understanding of their roles in heart development. Thirdly, an additional layer of regulation exists in the form of epigenetics. Cardiac TFs have been shown to interact with chromatin modifying factors, and loss of function of several histone modifying enzymes have been found to affect various aspects of cardiac development. The high degree of complexity in developmental regulation in vivo necessitates an approach which takes into account both genetic and epigenetic factors. Using a genomics approach and capitalizing on the advantages of zebrafish, we want to uncover genetic and epigenetic factors contributing to the process of heart development and elucidate their regulatory mechanism.


Core facility

One of the objectives of the FishMed project is development of the Zebrafish Core Facility. IIMCB’s Zebrafish Core Facility is now fully operational. The recruitment is complete – the leader of the facility and 4 technicians have been employed. The facility, opened in November 2012, comprises of a water plant, stand-alone unit (quarantine) and the main system manufactured by Tecniplast. The system can hold approximately 12000 of adult fish but further extension is planned. Since mid of 2014 in 564 tanks, 7000 fish representing 46 different lines of zebrafish are being bred. In the near future the system will be extended and more lines will be introduced.

Contact: aquarium@iimcb.gov.pl

YouTube