Longitudinal hair cortisol in bipolar disorder and a mechanism based on HPA dynamics.

Bipolar disorder (BD) is marked by fluctuating mood states over months to years, often with elevated cortisol levels. Elevated cortisol can also trigger mood episodes. Here, we combine longitudinal hair cortisol and mood measurements with mathematical modeling to provide a potential mechanistic link between cortisol and mood timescales in BD.

A synthetic differentiation circuit in Escherichia coli for suppressing mutant takeover.

Differentiation is crucial for multicellularity. However, it is inherently susceptible to mutant cells that fail to differentiate. These mutants outcompete normal cells by excessive self-renewal.

Tradeoffs in bacterial physiology determine the efficiency of antibiotic killing.

Antibiotic effectiveness depends on a variety of factors. While many mechanistic details of antibiotic action are known, the connection between death rate and bacterial physiology is poorly understood. A common observation is that death rate in antibiotics rises linearly with growth rate; however, it remains unclear how other factors, such as environmental conditions and whole-cell physiological properties, affect bactericidal activity.

Timescales of Human Hair Cortisol Dynamics.

Cortisol is a major human stress hormone, secreted within minutes of acute stress. Cortisol also has slower patterns of variation: a strong circadian rhythm and a seasonal rhythm. However, longitudinal cortisol dynamics in healthy individuals over timescales of months has rarely been studied.

A Bacterial Growth Law out of Steady State.

Bacterial growth follows simple laws in constant conditions. However, bacteria in nature often face fluctuating environments. We therefore ask whether there are growth laws that apply to changing environments.

Dynamic Proteomics of Herpes Simplex Virus Infection.

The cellular response to viral infection is usually studied at the level of cell populations. Currently, it remains an open question whether and to what extent cell-to-cell variability impacts the course of infection. Here we address this by dynamic proteomics-imaging and tracking 400 yellow fluorescent protein (YFP)-tagged host proteins in individual cells infected by herpes simplex virus 1.

Optimality and sub-optimality in a bacterial growth law.

Organisms adjust their gene expression to improve fitness in diverse environments. But finding the optimal expression in each environment presents a challenge. We ask how good cells are at finding such optima by studying the control of carbon catabolism genes in Escherichia coli.

Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.

In most conditions, glucose is the best carbon source for E. coli: it provides faster growth than other sugars, and is consumed first in sugar mixtures. Here we identify conditions in which E.

Hierarchy of non-glucose sugars in Escherichia coli.

Background: Understanding how cells make decisions, and why they make the decisions they make, is of fundamental interest in systems biology. To address this, we study the decisions made by E. coli on which genes to express when presented with two different sugars.

Linear superposition and prediction of bacterial promoter activity dynamics in complex conditions.

Bacteria often face complex environments. We asked how gene expression in complex conditions relates to expression in simpler conditions. To address this, we obtained accurate promoter activity dynamical measurements on 94 genes in E.

Promoter activity dynamics in the lag phase of Escherichia coli.

Background: Lag phase is a period of time with no growth that occurs when stationary phase bacteria are transferred to a fresh medium. Bacteria in lag phase seem inert: their biomass does not increase. The low number of cells and low metabolic activity make it difficult to study this phase.

Promoters maintain their relative activity levels under different growth conditions.

Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ~900 S. cerevisiae and ~1800 E.

The last generation of bacterial growth in limiting nutrient.

Background: Bacterial growth as a function of nutrients has been studied for decades, but is still not fully understood. In particular, the growth laws under dynamically changing environments have been difficult to explore, because of the rapidly changing conditions. Here, we address this challenge by means of a robotic assay and measure bacterial growth rate, promoter activity and substrate level at high temporal resolution across the entire growth curve in batch culture.

Surface growth of a motile bacterial population resembles growth in a chemostat.

The growth behavior in well-mixed bacterial cultures is relatively well understood. However, bacteria often grow in heterogeneous conditions on surfaces where their growth is dependent on spatial position, especially in the case of motile populations. For such populations, the relation between growth, motility and spatial position is unclear.

Mode of regulation and the insulation of bacterial gene expression.

A gene can be said to be insulated from environmental variations if its expression level depends only on its cognate inducers, and not on variations in conditions. We tested the insulation of the lac promoter of E. coli and of synthetic constructs in which the transcription factor CRP acts as either an activator or a repressor, by measuring their input function-their expression as a function of inducers-in different growth conditions.

A genome-wide analysis of promoter-mediated phenotypic noise in Escherichia coli.

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as "phenotypic noise.

Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.

Background: Gene regulation networks are made of recurring regulatory patterns, called network motifs. One of the most common network motifs is negative auto-regulation, in which a transcription factor represses its own production. Negative auto-regulation has several potential functions: it can shorten the response time (time to reach halfway to steady-state), stabilize expression against noise, and linearize the gene's input-output response curve.

Robust control of nitrogen assimilation by a bifunctional enzyme in E. coli.

Bacteria regulate the assimilation of multiple nutrients to enable growth. How is balanced utilization achieved, despite fluctuations in the concentrations of the enzymes that make up the regulatory circuitry? Here we address this question by studying the nitrogen system of E. coli.

Invariant distribution of promoter activities in Escherichia coli.

Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy.

The incoherent feed-forward loop can generate non-monotonic input functions for genes.

Gene regulation networks contain recurring circuit patterns called network motifs. One of the most common network motif is the incoherent type 1 feed-forward loop (I1-FFL), in which an activator controls both gene and repressor of that gene. This motif was shown to act as a pulse generator and response accelerator of gene expression.

Diverse two-dimensional input functions control bacterial sugar genes.

Cells respond to signals by regulating gene expression. The relation between the level of input signals and the transcription rate of the gene is called the gene's input function. Because most genes are regulated by more than one signal, the input functions are usually multidimensional.

A comprehensive library of fluorescent transcriptional reporters for Escherichia coli.

E. coli is widely used for systems biology research; there exists a need, however, for tools that can be used to accurately and comprehensively measure expression dynamics in individual living cells. To address this we present a library of transcriptional fusions of gfp to each of about 2,000 different promoters in E.