Modular interplay of transcription and translation

This project advances the understanding of the extraordinary success of microbes in adapting to diverse niches by modulating the interplay between the key cellular processes. This understanding is essential to manipulate microbial processes with applications ranging from bioenergy production to environmental sustainability and human health. For example, with such understanding the modification of how pathogens rapidly transition into a persistent-like state upon encountering a potentially lethal environment or the engineering of microbial strains for biotechnology applications and bioremediation, would be possible. Additionally, this project engages women, minorities, and systematically marginalized students and teachers, to develop and disseminate a standards-aligned high school curriculum module on adaptation and evolution in extreme environments. The development of a new high-school curriculum provides teaching with instruments optimized for teachers and relevant to current world issues and is accessible across all 50 states in the US and 144 countries worldwide.

The modular interplay of transcription and translation is foundational to the evolution of all organisms. Although the fundamental importance of ribosomes in protein synthesis has long been recognized, its capability as a regulatory element in gene expression has thus far been mostly overlooked. In order to manifest in phenotype, changes to modularity of a transcriptional regulatory program must have direct consequences on the coordinated synthesis and action of proteins (i.e., transcription factors, enzymes, etc.). Similarly, specialization of ribosomes requires parallel changes in transcriptional regulation so the specialized ribosomal subunits are made in the right environmental context, together with the pool of transcripts that need to be selectively translated. This research aims to elucidate how modular regulation of transcription generated through the expansion of a transcription factor family facilitates the coordinated recruitment of specialized ribosomes to pools of transcripts that encode functions required for adaptation to a new environment. The first aim investigates genome-wide changes in transcription, ribosome footprints and protein levels in the wild type and transcription factor mutants of H. salinarum during relevant environmental shifts. The second aim maps genome-wide binding locations and protein-protein interactions of transcription factors, and quantifies the composition and subunit stoichiometry of assembled ribosomal complexes in the same environmental contexts. The third aim characterizes transcriptome-wide and environment-specific consequences on ribosome recruitment and translation efficiency through rational reengineering of the transcriptional co-regulation of specialized ribosomal subunits. Finally, the fourth aim translates findings from this project to a high school classroom by developing a curriculum module on adaptation and evolution in environmental extremes. The successful execution of these aims allows elucidation of how heterogeneity is generated within the translation system and how a diverse population of ribosomes mediates environmentally relevant cellular phenotypes and physiological state transitions.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.