Project Grant 2624903

The National Science Foundation Division of Molecular and Cellular Biosciences awarded The Johns Hopkins University $337,841 on October 1, 2025, under the Biological Sciences program (CFDA 47.074) to quantify the prevalence and phenotypic consequences of transcriptional irreversibility in bacteria.

The project investigates how genetically identical bacterial cells achieve varied phenotypes through variations in gene expression, addressing how such variations can lead to antibiotic tolerance in some cells while others remain susceptible. The research expands understanding of irreversibility, hysteresis, and multistability to genomic scale by examining the time scales of reversibility and the prevalence of irreversibility following transient repression of all genes with known function in E. coli. The investigators will develop a light-inducible transient gene repression reagent called LIT-CRISPRI and combine experimental data with theory to establish expectations for the time scale of transcriptional, translational, and growth rate recovery. The project also includes development of an interactive series of lessons on mathematics in biology for high school students, distributed through teacher workshops.

Performance extends through January 31, 2027, with work performed in Baltimore, Maryland. Northwestern University serves as a sub-recipient, providing computational modeling, machine-learning-assisted analysis, and support for analysis of growth-measurement data, transcriptomic data, and whole-genome sequencing data. Northwestern's role includes modeling time scales governing transitions to and from perturbed states and implementing machine-learning approaches to identify factors governing the perturbation response. The sub-award to Northwestern was dated July 16, 2026.