Objectif
Epigenetics is a new and exciting area in biomedical sciences. It studies mitotically heritable chemical modifications of chromatin that are not associated with changes in the DNA sequence. Epigenetic modifications (EMs) affect the expression of genes, and therefore the phenotype of cells. Current views suggest that epigenetics reinforces cell fate stability. Indeed, EMs are essential for normal development and tissue homeostasis, and improper regulation may result in diseases like cancer. Despite the relatively good understanding of the role of epigenetics in mammals and flies, many questions are still open. They include the origin and distribution of EMs in animals, and how differences in epigenetic control mediate different life strategies among taxa. In particular, it is possible that traits like regenerative ability, growth plasticity, senescence and resistance to malignancy, which are differentially distributed among animal groups, are primarily mediated by taxon-specific EMs. We propose to test this hypothesis by studying the role of epigenetics in stem cell fate determination in the cnidarian Hydractinia echinata, an animal model that occupies a phylogenetically pivotal position at the base of the animal kingdom,
and is genetically tractable and susceptible to genetically manipulation. We will use a genome wide approach to map DNA methylation and histone modification sites in the Hydractinia genome. We will then analyze the specific utilization of EMs, comparing stem cells with terminally differentiated somatic cells. Finally, we will use gain and loss of function experiments to study the specific role of selected EM genes in different contexts in the Hydractinia life history. This project will provide insight into the mechanisms that mediates stem cell decision-making and why they are more versatile in basal invertebrates. Our results will impact not only such fields as evolutionary, cell and developmental biology, but also regenerative medicine and cancer.
Champ scientifique
Appel à propositions
FP7-PEOPLE-2013-IIF
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Régime de financement
MC-IIF - International Incoming Fellowships (IIF)Coordinateur
H91 Galway
Irlande