Life on earth is shaped by dynamic interactions of molecules, pathways, cells, organisms, and ecosystems. Our research began with the studies of protein-protein interactions underlying protein ubiquitination, a form of post-translational modification that regulates the functions of a large variety of protein substrates in eukaryotes. We initially focused on a superfamily of protein complex machineries, the cullin-RING ubiquitin ligases, but were soon led by ubiquitin to unexpected new research areas. Our ongoing studies now span several interwoven domains of interests and will continue to venture into the vast unknown of biology and the promising avenues of therapeutics discovery.