How the genome is co-ordinately regulated during development is one of the major unanswered questions in modern biology.
We are exploring this issue by means of comparative and functional approaches, with the aim of understanding how gene regulatory networks were assembled during evolution and how this determines their function. We are particularly interested in understanding the function of the gene regulatory network that controls embryonic pluripotency in the mouse embryo. Comparison with other vertebrates to determine the degree of conservation of these genes and their interactions shows that the core pluripotency factors (Oct4-Sox2-Nanog) were newly assembled into a network in the mammalian lineage and that downstream target genes of this core set were recruited through the appearance of novel enhancer elements. We are also exploring the role of miRNAs as a second layer of regulation in the establishment of extraembryonic stem cell populations.
Another area of interest is the potential regulatory function during development of intergenic genomic regions that have been identified with human diseases through genome-wide studies. These studies include analysis of the genomic regions associated with increased risk of type II diabetes and obesity as well as investigation into the role of p63 and its downstream regulatory network in human disease.
Regarding scientific networks, Miguel Manzanares participates in the EuroSystem project as an Associate Principal Investigator.