Keeping Signals Straight: How Cells Process Information and Make Decisions

As we become increasingly dependent on electronic information-processing systems at home and work, it’s easy to lose sight of the fact that our very survival depends on highly complex biological information-processing systems. Each of the trillions of cells that form the human body has the ability to detect and respond to a wide range of stimuli and inputs, using an extraordinary set of signaling proteins to process this information and make decisions accordingly. Indeed, cells in all organisms rely on these signaling proteins to survive and proliferate in unpredictable and sometimes rapidly changing environments. But how exactly do these proteins relay information within cells, and how do they keep a multitude of incoming signals straight? Here, I describe recent efforts to understand the fidelity of information flow inside cells. This work is providing fundamental insight into how cells function. Additionally, it may lead to the design of novel antibiotics that disrupt the signaling of pathogenic bacteria or it could help to guide the treatment of cancer, which often involves information-processing gone awry inside human cells

Boltzmann and hydrodynamic description for self-propelled particles

We study analytically the emergence of spontaneous collective motion within large bidimensional groups of self-propelled particles with noisy local interactions, a schematic model for assemblies of biological organisms. As a central result, we derive from the individual dynamics the hydrodynamic equations for the density and velocity fields, thus giving a microscopic foundation to the phenomenological equations used in previous approaches. A homogeneous spontaneous motion emerges below a transition line in the noise-density plane. Yet, this state is shown to be unstable against spatial perturbations, suggesting that more complicated structures should eventually appear.Comment: 4 pages, 3 figures, final versio

New approaches to understanding the spatial organization of bacterial genomes

In all organisms, chromosomal DNA must be compacted nearly three orders of magnitude to fit within the limited volume of a cell. However, chromosomes cannot be haphazardly packed, and instead must adopt structures compatible with numerous cellular processes, including DNA replication, chromosome segregation, recombination, and gene expression. Recent technical advances have dramatically enhanced our understanding of how chromosomes are organized in vivo and have begun to reveal the mechanisms and forces responsible. Here, we review the current arsenal of techniques used to query chromosome structure, focusing first on single-cell fluorescence microscopy approaches that directly examine chromosome structure and then on population-averaged biochemical methods that infer chromosome structure based on the interaction frequencies of different loci. We describe the power of these techniques, highlighting the major advances they have produced while also discussing their limitations.National Institutes of Health (U.S.) (Grant R01GM082899)Gordon and Betty Moore FoundationLife Sciences Research Foundation (Fellowship

Bacterial Chromosome Organization and Segregation

If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.National Institutes of Health (U.S.) (Grant R01GM082899

Characteristics of schools with and without Gay-Straight Alliances

Research shows that Gay-Straight Alliances (GSAs) are associated with school climate and student well-being, but it is unclear what school characteristics may account for some of these findings. The current study describes characteristics of schools with and without GSAs. Using a population-based sample of 1,360 California public high schools, inferential statistics show that schools with larger enrollment, more experienced teachers, and lower pupil/teacher ratios were more likely to have GSAs. In addition, among schools with GSAs, larger enrollment, more experienced teachers, fewer socioeconomically disadvantaged students, and higher academic achievement are among the factors related to a longer presence of GSAs. Implications for GSA and policy implementation, as well as the importance of accounting for school characteristics in research on GSAs are discussed

Youth Empowerment and High School Gay-Straight Alliances

In the field of positive youth development programs, “empowerment” is used interchangeably with youth activism, leadership, civic participation and self-efficacy. However, few studies have captured what empowerment means to young people in diverse contexts. This article explores how youth define and experience empowerment in youth-led organizations characterized by social justice goals: high school Gay-Straight Alliances (GSAs). Through focus group interviews, fifteen youth leaders of GSAs from different regions of California explain what they think empowerment means and how they became empowered through their involvement with the GSA. Youth describe three inter-related dimensions of empowerment: personal empowerment, relational empowerment, and strategic empowerment through having and using knowledge. When these three dimensions are experienced in combination, GSA leaders have the potential for individual and collective empowerment as agents of social change at school. By understanding these youth\u27s perspectives on the meanings of empowerment, this article clarifies the conceptual arena for future studies of socially marginalized youth and of positive youth development

Onset of collective and cohesive motion

We study the onset of collective motion, with and without cohesion, of groups of noisy self-propelled particles interacting locally. We find that this phase transition, in two space dimensions, is always discontinuous, including for the minimal model of Vicsek et al. [Phys. Rev. Lett. {\bf 75},1226 (1995)] for which a non-trivial critical point was previously advocated. We also show that cohesion is always lost near onset, as a result of the interplay of density, velocity, and shape fluctuations.Comment: accepted for publication in Phys. Rev. Let

A Bacterial Toxin Inhibits DNA Replication Elongation through a Direct Interaction with the β Sliding Clamp

Toxin-antitoxin (TA) systems are ubiquitous on bacterial chromosomes, yet the mechanisms regulating their activity and the molecular targets of toxins remain incompletely defined. Here, we identify SocAB, an atypical TA system in Caulobacter crescentus. Unlike canonical TA systems, the toxin SocB is unstable and constitutively degraded by the protease ClpXP; this degradation requires the antitoxin, SocA, as a proteolytic adaptor. We find that the toxin, SocB, blocks replication elongation through an interaction with the sliding clamp, driving replication fork collapse. Mutations that suppress SocB toxicity map to either the hydrophobic cleft on the clamp that binds DNA polymerase III or a clamp-binding motif in SocB. Our findings suggest that SocB disrupts replication by outcompeting other clamp-binding proteins. Collectively, our results expand the diversity of mechanisms employed by TA systems to regulate toxin activity and inhibit bacterial growth, and they suggest that inhibiting clamp function may be a generalizable antibacterial strategy.Howard Hughes Medical Institute (Summer Medical Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.) (R01GM082899

A DNA Damage-Induced, SOS-Independent Checkpoint Regulates Cell Division in Caulobacter crescentus

Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.National Institutes of Health (U.S.) (Grant R01GM082899)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Determinants of Homodimerization Specificity in Histidine Kinases

Two-component signal transduction pathways consisting of a histidine kinase and a response regulator are used by prokaryotes to respond to diverse environmental and intracellular stimuli. Most species encode numerous paralogous histidine kinases that exhibit significant structural similarity. Yet in almost all known examples, histidine kinases are thought to function as homodimers. We investigated the molecular basis of dimerization specificity, focusing on the model histidine kinase EnvZ and RstB, its closest paralog in Escherichia coli. Direct binding studies showed that the cytoplasmic domains of these proteins each form specific homodimers in vitro. Using a series of chimeric proteins, we identified specificity determinants at the base of the four-helix bundle in the dimerization and histidine phosphotransfer domain. Guided by molecular coevolution predictions and EnvZ structural information, we identified sets of residues in this region that are sufficient to establish homospecificity. Mutating these residues in EnvZ to the corresponding residues in RstB produced a functional kinase that preferentially homodimerized over interacting with EnvZ. EnvZ and RstB likely diverged following gene duplication to yield two homodimers that cannot heterodimerize, and the mutants we identified represent possible evolutionary intermediates in this process.National Institutes of Health (U.S.) (Award GM067681)National Science Foundation (U.S.) (CAREER Grant)National Science Foundation (U.S.). Graduate Research Fellowshi