The main objective of the international training network UPStream is the training of a novel generation of European scientist in a critical and complex field of modern biology: the understanding of the regulation of the UPS and its potential use for drug development. The importance of this process is illustrated by the imperious necessity to destroy certain proteins during several phases of the cell cycle in order to progress to the next phase. The biochemical process of ubiquitylation is an efficient way to label proteins that will be targeted to degradation by the proteasome at the right time and cellular compartment, according to the cell necessities. In addition, this post-translational modification also offers to the cell the possibility to control other processes related or not to proteolytic functions. Indeed, the attachment of ubiquitin (Ub) or ubiquitin-like (UBL) molecules such as SUMO and NEDD8 does not always result in proteolysis, but can induce conformational and/or interaction changes driving a large diversity of effects. Considering the interconnectivity among Ub and UBL molecules, we end up with an extremely complex system regulating protein activity and stability. Given the implications of the ubiquitin proteasome system (UPS) in many essential cellular processes, the technology required to study this system is very diverse. As part of the proposed network the latest technological developments (please see implementation) will be used to explore chemical, biochemical, molecular, developmental and genetic aspects of the UPS. This research area has become an area of investigation by itself, very attractive for fundamental scientists as well as for the pharmaceutical industry aiming to identify potential targets for drug development to be used in many diseases where this system has been shown to be vital.