Our work focuses on the process of ubiquitylation, the process cells use to label unwanted proteins for disposal. Attachment of the molecule ubiquitin to a protein communicates to the cellular infrastructure that the protein should be degraded in an ordered process. Mis-regulation of the ubiquitin signaling pathway is associated with both cancers and neurodegenerative disorders therefore it is critical to understand how this process is controlled. Ubiquitylation requires three distinct proteins, E1, E2 and E3. While cells contain many different E2-class proteins, and hundreds of different E3-class proteins, dogma for the last 25 years stated that there was a single E1 enzyme. Recently, through biochemical and genetic experiments we discovered a new E1 ubiquitin-activating enzyme, Uba6. The lab is conducting experiments to better characterize a new process of protein disposal elucidated by his discovery of a new E1, through bioinformatics, RNAi, proteomic, and biochemical approaches.