Blocking uncertain mispriming errors of PCR.

The polymerase chain reaction (PCR) plays a central role in genetic engineering and is routinely used in various applications, from biological and medical research to the diagnosis of viral infections. PCR is an extremely sensitive method for detecting target DNA sequences, but it is substantially error prone. In particular, the mishybridization of primers to contaminating sequences can result in false positives for virus tests.

Thermodynamic bounds on time-reversal asymmetry.

Quantifying irreversibility of a system using finite information constitutes a major challenge in stochastic thermodynamics. We introduce an observable that measures the time-reversal asymmetry between two states after a given time lag. Our central result is a bound on the time-reversal asymmetry in terms of the total cycle affinity driving the system out of equilibrium.

Genome replication in asynchronously growing microbial populations.

Biological cells replicate their genomes in a well-planned manner. The DNA replication program of an organism determines the timing at which different genomic regions are replicated, with fundamental consequences for cell homeostasis and genome stability. In a growing cell culture, genomic regions that are replicated early should be more abundant than regions that are replicated late.

Error-suppression mechanism of PCR by blocker strands.

The polymerase chain reaction (PCR) is a central technique in biotechnology. Its ability to amplify a specific target region of a DNA sequence has led to prominent applications, including virus tests, DNA sequencing, genotyping, and genome cloning. These applications rely on the specificity of the primer hybridization and therefore require effective suppression of hybridization errors.

Coalescent dynamics of planktonic communities.

Planktonic communities are extremely diverse and include a vast number of rare species. The dynamics of these rare species is best described by individual-based models. However, individual-based approaches to planktonic diversity face substantial difficulties, due to the large number of individuals required to make realistic predictions.

Speed variations of bacterial replisomes.

Replisomes are multi-protein complexes that replicate genomes with remarkable speed and accuracy. Despite their importance, their dynamics is poorly characterized, especially in vivo. In this paper, we present an approach to infer the replisome dynamics from the DNA abundance distribution measured in a growing bacterial population.

Optimization and Fabrication of Multi-Level Microchannels for Long-Term Imaging of Bacterial Growth and Expansion.

Bacteria are unicellular organisms whose length is usually around a few micrometers. Advances in microfabrication techniques have enabled the design and implementation of microdevices to confine and observe bacterial colony growth. Microstructures hosting the bacteria and microchannels for nutrient perfusion usually require separate microfabrication procedures due to different feature size requirements.

Population genetics in microchannels.

SignificanceMany microbial populations proliferate in small channels. In such environments, reproducing cells organize in parallel lanes. Reproducing cells shift these lanes, potentially expelling other cells from the channel.

Search and Localization Dynamics of the CRISPR-Cas9 System.

The CRISPR-Cas9 system acts as the prokaryotic immune system and has important applications in gene editing. The protein Cas9 is one of its crucial components. The role of Cas9 is to search for specific target sequences on the DNA and cleave them.

Enhanced Mutation Rate, Relaxed Selection, and the "Domino Effect" are associated with Gene Loss in Blattabacterium, A Cockroach Endosymbiont.

Intracellular endosymbionts have reduced genomes that progressively lose genes at a timescale of tens of million years. We previously reported that gene loss rate is linked to mutation rate in Blattabacterium, however, the mechanisms causing gene loss are not yet fully understood. Here, we carried out comparative genomic analyses on the complete genome sequences of a representative set of 67 Blattabacterium strains, with sizes ranging between 511 and 645 kb.

Generalized Euler-Lotka equation for correlated cell divisions.

Cell division times in microbial populations display significant fluctuations that impact the population growth rate in a nontrivial way. If fluctuations are uncorrelated among different cells, the population growth rate is predicted by the Euler-Lotka equation, which is a classic result in mathematical biology. However, cell division times can be significantly correlated, due to physical properties of cells that are passed through generations.

Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge.

Ocean currents promote rare species diversity in protists.

Oceans host communities of plankton composed of relatively few abundant species and many rare species. The number of rare protist species in these communities, as estimated in metagenomic studies, decays as a steep power law of their abundance. The ecological factors at the origin of this pattern remain elusive.

Increased Mutation Rate Is Linked to Genome Reduction in Prokaryotes.

The evolutionary processes that drive variation in genome size across the tree of life remain unresolved. Effective population size (N) is thought to play an important role in shaping genome size [1-3]-a key example being the reduced genomes of insect endosymbionts, which undergo population bottlenecks during transmission [4]. However, the existence of reduced genomes in marine and terrestrial prokaryote species with large N indicate that genome reduction is influenced by multiple processes [3].

Hyperaccurate currents in stochastic thermodynamics.

Thermodynamic observables of mesoscopic systems can be expressed as integrated empirical currents. Their fluctuations are bound by thermodynamic uncertainty relations. We introduce the hyperaccurate current as the integrated empirical current with the least fluctuations in a given nonequilibrium system.

Assembly of heteropolymers via a network of reaction coordinates.

In biochemistry, heteropolymers encoding biological information are assembled out of equilibrium by sequentially incorporating available monomers found in the environment. Current models of polymerization treat monomer incorporation as a sequence of discrete chemical reactions between intermediate metastable states. In this paper, we use ideas from reaction rate theory and describe nonequilibrium assembly of a heteropolymer via a continuous reaction coordinate.

Error-Speed Correlations in Biopolymer Synthesis.

Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical processes aided by enzymes. The performance of these enzymes is usually characterized in terms of their average error rate and speed. However, because of thermal fluctuations in these single-molecule processes, both error and speed are inherently stochastic quantities.

Bet-hedging strategies in expanding populations.

In ecology, species can mitigate their extinction risks in uncertain environments by diversifying individual phenotypes. This observation is quantified by the theory of bet-hedging, which provides a reason for the degree of phenotypic diversity observed even in clonal populations. Bet-hedging in well-mixed populations is rather well understood.

Arcsine Laws in Stochastic Thermodynamics.

We show that the fraction of time that a thermodynamic current spends above its average value follows the arcsine law, a prominent result obtained by Lévy for Brownian motion. Stochastic currents with long streaks above or below their average are much more likely than those that spend similar fractions of time above and below their average. Our result is confirmed with experimental data from a Brownian Carnot engine.

Evolution of Complex Asexual Reproductive Strategies in Jellyfish.

Many living organisms in terrestrial and aquatic ecosystems rely on multiple reproductive strategies to reduce the risk of extinction in variable environments. Examples are provided by the polyp stage of several bloom-forming jellyfish species, which can reproduce asexually using different budding strategies. These strategies broadly fall into three categories: (1) fast localized reproduction, (2) dormant cysts, or (3) motile and dispersing buds.

Mapping of uncertainty relations between continuous and discrete time.

Lower bounds on fluctuations of thermodynamic currents depend on the nature of time, discrete or continuous. To understand the physical reason, we compare current fluctuations in discrete-time Markov chains and continuous-time master equations. We prove that current fluctuations in the master equations are always more likely, due to random timings of transitions.

Energetic funnel facilitates facilitated diffusion.

Transcription factors (TFs) are able to associate to their binding sites on DNA faster than the physical limit posed by diffusion. Such high association rates can be achieved by alternating between three-dimensional diffusion and one-dimensional sliding along the DNA chain, a mechanism-dubbed facilitated diffusion. By studying a collection of TF binding sites of Escherichia coli from the RegulonDB database and of Bacillus subtilis from DBTBS, we reveal a funnel in the binding energy landscape around the target sequences.

Generic Properties of Stochastic Entropy Production.

We derive an Itô stochastic differential equation for entropy production in nonequilibrium Langevin processes. Introducing a random-time transformation, entropy production obeys a one-dimensional drift-diffusion equation, independent of the underlying physical model. This transformation allows us to identify generic properties of entropy production.

Competition between fast- and slow-diffusing species in non-homogeneous environments.

We study an individual-based model in which two spatially distributed species, characterized by different diffusivities, compete for resources. We consider three different ecological settings. In the first, diffusing faster has a cost in terms of reproduction rate.