Proteins involved in major human diseases undergo significant posttranslational modification (PTM). PTMs relay chemical signals that alter cell fate and gene expression. Certain signals lead to diseases like cancer or neurodegeneration, while others do not. To investigate the role of these protein modifications in signalling, epigenetic, and oxidative stress pathways relevant to cancer, the proposed research will establish systems that synthesize proteins with multiple hardwired PTMs. The technology will be fundamental and not limited to the projects outlined here, because PTMs are ubiquitous in nature and play important roles in diverse biological systems from human cells to microorganisms.