SP 5

Cross-species model analysis of heart disease regulation

The project aims at enhancing the understanding of genetic factors controling heart development and homeostatis. Using existing knowledge on heart genes and new transcriptomic profiles of heart failure phenotypes provided by the other projects of SYMBOL-HF we want to identify correlations between genes, suggest links and crosstalk between pathways, upstream and downstream relations between gene interactions.

Ultimately, we want to construct a more complete gene regulatory network of heart development and homeostasis then solely based on published data. This heart gene regulatory network will reproduce known gene expression profiles of observed heart failure phenotypes and predict outcomes of new mutants.

The other subprojects will provide data from different vertebrate species. Zebrafish models (SP1) allow a rapid generation of data as a heart failure phenotype can be observed within days after fertilization. Mouse models (SP2) serve as a mammal experimental system. Human samples (SP3) allow establishing correspondences between clinical conditions and measurements from animals. Therefore, this project will additionally focus on an interspecies comparison and integrate data from various sources in a joint network model.

Finally, based on the extended heart gene regulatory network, the subproject will suggest gene targets for recovering heart failure phenotypes and rank small compounds for screening and assessment as possible treatment methods.