During my PhD training performed at Northwestern University (Evanston, USA) as a visiting graduate student, I discovered two new yeast genes, SIN3 and RPD3, and demonstrated their function in global transcriptional regulation. Together with the subsequent biochemical identification of histone deacetylase as the product of RPD3, my work helped confirm the Allfrey hypothesis which concerns the role of histone modifications in transcriptional regulation, widely considered one of the major events that sparked the field of modern epigenetics. Since the mid 90s, I have focused my attention on understanding complex macromolecular networks and systems operating within cells. My main hypothesis is that cells can be better understood as a wiring diagram of dynamic molecular interactions and that perturbations of such interactions underlie most genotype-phenotype relationships. Originally trained as a bioengineer and a geneticist, I pioneered the concept of “interactome network modeling”, which is based on interdisciplinary strategies developed with collaborators from the fields of physics, computer science, mathematics, genomics and human genetics. Together, we have discovered fundamental systems properties in the human interactome network and are now starting to unravel fundamental relationships between cellular systems and human disease.