Gametic Epigenetics Consortium against Obesity (GECKO)

1. Nutritional intervention studies
   We are conducting several nutritional intervention studies, including in mice, pigs and humans. The aim of these projects is to precisely define the effect of certain diets (both in terms of type of food and caloric intake) on the gametic and somatic epigenome of fathers and their offspring. In other words, how does diet affect the epigenetic marks that are passed on to offspring?
   
   
2. Comparative epigenomics
   We collaborate with Copenhagen Zoo and Taronga Zoo in Sydney to collect sperm samples from many different animal species. The aim of the study is to produce an atlas of sperm epigenomes from a range of species, including primates and humans, so we can better understand how epigenomes vary between species, and which particular regions of epigenetic variation are conserved across animals. This study stemmed from the observations made by the Barrès group, that there are ‘hotspots’ of epigenetic variation on the genome (GHEVs) and that these tend to cluster around genes associated with brain development and behaviour. We hope to uncover whether GHEVs are conserved across species or unique to humans.
   
   
3. Functional genomics
   An outstanding question connected to epigenetic inheritance is how epigenetic changes in gametes affect subsequent cell differentiation of the developing embryo.
   With expertise from our partners at the University of Chicago, this project seeks to answer this question using DNA conformation capture assays to study in somatic cells of the next generation offspring the epigenetic status of GHEV-containing regions. We will also use embryonic stem cells and CRISPR-Cas9 to methylate target genes and observe differences in cell differentiation. From this, we can draw conclusions about the effect of specific methylation sites on the resulting phenotype.
   

We are funded by a Novo Nordisk Foundation Challenge Grant 33754.