Genetic Regulation of Organ Development and Regeneration

The PI of this offer is the coordinator of the Horizon2020 project REANIMA: New-generation cardiac therapeutic strategies directed to the activation of endogenous regenerative mechanisms.  Within this project, a Master thesis is offered to work in the following task: Use of an ex vivo neonatal cardiomyocyte culture system to study the relationships between  different pro-regenerative extrinsic and intrinsic treatments.  Manipulation of the pathways will be rapidly achieved by the use of direct activation or inhibition of the pathways using established methodologies, including purified proteins, modified mRNAs, RNA interference or viral expression, depending on the specific factor to analyse. We will perform RNAseq transcriptomic analysis of these functional models. The data obtained from RNAseq will allow us to formulate hypotheses about the hierarchy and connectivity of the pathways. We will first study relationships between pro-regenerative environmental cues, including those already known (Agrin) and REANIMA newly identified extracellular signals.  In the same context, we will analyse the relationships among the main known intrinsic pathways regulating cardiomyocyte proliferation and competition (ErbB2, YAP, Wnt/beta-catenin, Notch, Myc).  RNAseq analysis from the functional models studied will be used for the design and execution of epistatic analyses, in which we will assess cardiomyocyte proliferation and maturation by studying binucleation, cytokinesis, sarcomere assembly and competitive ability.