An optimal regulation of fluxes dictates microbial growth in and out of steady state.

Effective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic regulation of this resource partitioning.

Anthroponumbers.org: A quantitative database of human impacts on Planet Earth.

The Human Impacts Database (www.anthroponumbers.org) is a curated, searchable resource housing quantitative data relating to the diverse anthropogenic impacts on our planet, with topics ranging from sea-level rise to livestock populations, greenhouse gas emissions, fertilizer use, and beyond.

Fundamental limits on the rate of bacterial growth and their influence on proteomic composition.

Despite abundant measurements of bacterial growth rate, cell size, and protein content, we lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we estimate the basic requirements and physical constraints on steady-state growth by considering key processes in cellular physiology across a collection of Escherichia coli proteomic data covering ≈4,000 proteins and 36 growth rates. Our analysis suggests that cells are predominantly tuned for the task of cell doubling across a continuum of growth rates; specific processes do not limit growth rate or dictate cell size.

First-principles prediction of the information processing capacity of a simple genetic circuit.

Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hypothesized to have consequences for how cells are able to survive in changing environments. Recent work has explored the use of information theory as a framework to understand the accuracy with which cells can ascertain the state of their surroundings.

Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.

Developing lymphocytes of jawed vertebrates cleave and combine distinct gene segments to assemble antigen-receptor genes. This process called V(D)J recombination that involves the RAG recombinase binding and cutting recombination signal sequences (RSSs) composed of conserved heptamer and nonamer sequences flanking less well-conserved 12- or 23-bp spacers. Little quantitative information is known about the contributions of individual RSS positions over the course of the RAG-RSS interaction.

Theoretical investigation of a genetic switch for metabolic adaptation.

Membrane transporters carry key metabolites across the cell membrane and, from a resource standpoint, are hypothesized to be produced when necessary. The expression of membrane transporters in metabolic pathways is often upregulated by the transporter substrate. In E.

Predictive shifts in free energy couple mutations to their phenotypic consequences.

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response.

Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene Expression.

It is tempting to believe that we now own the genome. The ability to read and rewrite it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles' heel exposed by all of the genomic data that has accrued: We still do not know how to interpret them.

Connecting the Dots between Mechanosensitive Channel Abundance, Osmotic Shock, and Survival at Single-Cell Resolution.

Rapid changes in extracellular osmolarity are one of many insults microbial cells face on a daily basis. To protect against such shocks, and other microbes express several types of transmembrane channels that open and close in response to changes in membrane tension. In , one of the most abundant channels is the mechanosensitive channel of large conductance (MscL).

Tuning Transcriptional Regulation through Signaling: A Predictive Theory of Allosteric Induction.

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response.