Functional genomic research in mammals has been hampered by the lack of appropriate study models. Thus, specific aspects of gene regulation in vivo remain unknown, as does the genetic causes underlying various human diseases. The creation of such animal models, which are tailor-made transgenic mice, has necessitated the development of a new tool, the viral transgenesis platform.

This platform provides modified viruses that function as carriers and deliver selected genes to mice germinal cells. To achieve this, the scientists synthesize customized viral vectors derived from HIV genetic material, to which they add selected genes. The engineered viral particles will then be used to infect mice oocytes, which will express the genes of interest. The transgenic mice thus obtained are used to investigate the function and regulation of specific genes, as well as their impact on human pathologies.

Several projects of this work package aim at unveiling molecular events occurring during embryonic development. One study focuses on a family of human epigenetic repressors. Although these factors mediate gene inhibition, their different roles and target genes remain essentially unknown. Another group is interested in portions of the genome that are highly conserved among mammalian species, although they do not code for any protein. Whether and how they control “developmental” genes are the aspects under scrutiny. In a third project, we are investigating the finely tuned and complex regulation of the architect genes named Hox, which are essential for coordinating body patterning.

Viral vectors are also used to study the expression of clock genes. The latter constitute the molecular machinery of our internal clock, composed of a central “pacemaker” in the brain, as well as subordinate oscillators present in most of our cells. Other labs take advantage of the transgenesis platform to decipher the dialogs occurring between different tissues during skin wound healing, tumour growth and placental development. In particular, they examine the involvement of transcription factors named PPAR, which are important players in the development and homeostasis of the organism. Molecular exchanges of information are also monitored at the level of the mouse olfactory system, in neurons detecting pheromones. These molecules are essential for mammals to interact adequately with one another. While many pheromones receptors have been discovered, almost none of their ligands have been identified so far.

Another main research tool of this work package was engineered to obtain very efficient transgenesis at predetermined locations of the DNA. This new technology, developed to perform functional analyses of the genome of the fly Drosophila, will also be adapted to the mouse.