Bacterial transcription is mostly regulated by transcription factors (TFs); however, expression in
minimal bacteria shows an increased relevance of TF-independent regulation elements as
consequence of their reduced number of TFs. This project aims to disentangle the transcriptional
complexity of reduced-genome bacteria building a comprehensive computational model including any possible regulatory component. Using a rule-based modular design, this model allows the study of transcriptional regulation network hierarchy, being easily modifiable, scalable and combinable with other submodels in a new generation of whole-cell models. These improved whole-cell versions,implemented together concepts like non-annotated small proteins and quantitative essentiality, will provide a step ahead in the rational design of minimal bacteria with multiple biotechnological and biomedical applications.