arXiv subjects

Ido Golding

Publications and source records attributed to Ido Golding.

10 recordsLinked to original sources

arXiv2026

Transcription rate dynamics and RNA copy number noise: General relations and data-driven predictions

Stochastic models of gene expression typically begin with a microscopic model of transcription and propagate its statistics to the RNA distribution. Here we develop a doubly stochastic framework in which RNA production is Poisson conditional on a time-varying transcription rate $\lambda(t)$. For RNA lifetimes drawn independently from an arbitrary finite-mean distribution, we derive the RNA Fano factor in terms of the lifetime survival function and the autocovariance of $\lambda(t)$. For a Poisson degradation process with rate $\mu$, the survival kernel provides an exponential temporal filter, and the result depends only on the mean, variance, and normalized autocorrelation of $\lambda(t)$. These quantities may be calculated from an explicit rate model or, under ergodicity and adequate sampling, estimated from a sufficiently long rate trajectory. We validate the data-driven estimator using simulated transcription-rate trajectories, without supplying the known autocorrelation to the estimator. We also obtain exact analytical results for transcription-rate dynamics modeled by a discrete M/M/1 process and by drift-diffusion with reflecting, periodic, or first-passage-reset boundaries, and verify each result by direct simulation of the coupled transcription-rate and RNA copy-number processes.

physics.bio-ph↗

arXiv2023

Gene expression in growing cells: A biophysical primer

Cell growth and gene expression, essential elements of all living systems, have long been the focus of biophysical interrogation. Advances in single-cell methods have invigorated theoretical studies into these processes. However, until recently, there was little dialog between the two areas of study. Most theoretical models for gene regulation assumed gene activity to be oblivious to the progression of the cell cycle between birth and division. But there are numerous ways in which the periodic character of all cellular observables can modulate gene expression. The molecular factors required for transcription and translation increase in number during the cell cycle, but are also diluted due to the continuous increase in cell volume. The replication of the genome changes the dosage of those same cellular players but also provides competing targets for regulatory binding. Finally, cell division reduces their number again, and so forth. Stochasticity is inherent to all these biological processes, manifested in fluctuations in the synthesis and degradation of new cellular components as well as the random partitioning of molecules at each cell division. The notion of gene expression as stationary is thus hard to justify. In this review, we survey the emerging paradigm of cell-cycle regulated gene expression, with an emphasis on the global expression patterns rather than gene-specific regulation. We discuss recent experimental reports where cell growth and gene expression were simultaneously measured in individual cells, providing first glimpses into the coupling between the two. While the experimental findings, not surprisingly, differ among genes and organisms, several theoretical models have emerged that attempt to reconcile these differences and form a unifying framework for understanding gene expression in growing cells.

q-bio.SC↗

arXiv2008

Lambda-prophage induction modeled as a cooperative failure mode of lytic repression

We analyze a system-level model for lytic repression of lambda-phage in E. coli using reliability theory, showing that the repressor circuit comprises 4 redundant components whose failure mode is prophage induction. Our model reflects the specific biochemical mechanisms involved in regulation, including long-range cooperative binding, and its detailed predictions for prophage induction in E. coli under ultra-violet radiation are in good agreement with experimental data.

q-bio.MN↗

arXiv2008

Quantitative transcription factor binding kinetics at the single-molecule level

We have investigated the binding interaction between the bacteriophage lambda repressor CI and its target DNA using total internal reflection fluorescence microscopy. Large, step-wise changes in the intensity of the red fluorescent protein fused to CI were observed as it associated and dissociated from individually labeled single molecule DNA targets. The stochastic association and dissociation were characterized by Poisson statistics. Dark and bright intervals were measured for thousands of individual events. The exponential distribution of the intervals allowed direct determination of the association and dissociation rate constants, ka and kd respectively. We resolved in detail how ka and kd varied as a function of 3 control parameters, the DNA length L, the CI dimer concentration, and the binding affinity. Our results show that although interaction with non-operator DNA sequences are observable, CI binding to the operator site is not dependent on the length of flanking non-operator DNA.

q-bio.QM↗

arXiv1999

Modeling branching and chiral colonial patterning of lubricating bacteria

In nature, microorganisms must often cope with hostile environmental conditions. To do so they have developed sophisticated cooperative behavior and intricate communication capabilities, such as: direct cell-cell physical interactions via extra-membrane polymers, collective production of extracellular "wetting" fluid for movement on hard surfaces, long range chemical signaling such as quorum sensing and chemotactic (bias of movement according to gradient of chemical agent) signaling, collective activation and deactivation of genes and even exchange of genetic material. Utilizing these capabilities, the colonies develop complex spatio-temporal patterns in response to adverse growth conditions. We present a wealth of branching and chiral patterns formed during colonial development of lubricating bacteria (bacteria which produce a wetting layer of fluid for their movement). Invoking ideas from pattern formation in non-living systems and using ``generic'' modeling we are able to reveal novel survival strategies which account for the salient features of the evolved patterns. Using the models, we demonstrate how communication leads to self-organization via cooperative behavior of the cells. In this regard, pattern formation in microorganisms can be viewed as the result of the exchange of information between the micro-level (the individual cells) and the macro-level (the colony). We mainly review known results, but include a new model of chiral growth, which enables us to study the effect of chemotactic signaling on the chiral growth. We also introduce a measure for weak chirality and use this measure to compare the results of model simulations with experimental observations.

cond-mat↗

arXiv1998

Spatio-selection in Expanding Bacterial Colonies

Segregation of populations is a key question in evolution theory. One important aspect is the relation between spatial organization and the population's composition. Here we study a specific example -- sectors in expanding bacterial colonies. Such sectors are spatially segregated sub-populations of mutants. The sectors can be seen both in disk-shaped colonies and in branching colonies. We study the sectors using two models we have used in the past to study bacterial colonies -- a continuous reaction-diffusion model with non-linear diffusion and a discrete ``Communicating Walkers'' model. We find that in expanding colonies, and especially in branching colonies, segregation processes are more likely than in a spatially static population. One such process is the establishment of stable sub- population having neutral mutation. Another example is the maintenance of wild-type population along side with sub-population of advantageous mutants. Understanding such processes in bacterial colonies is an important subject by itself, as well as a model system for similar processes in other spreading populations.

cond-mat↗

arXiv1998

Lubricating Bacteria Model for Branching growth of Bacterial Colonies

Various bacterial strains (e.g. strains belonging to the genera Bacillus, Paenibacillus, Serratia and Salmonella) exhibit colonial branching patterns during growth on poor semi-solid substrates. These patterns reflect the bacterial cooperative self-organization. Central part of the cooperation is the collective formation of lubricant on top of the agar which enables the bacteria to swim. Hence it provides the colony means to advance towards the food. One method of modeling the colonial development is via coupled reaction-diffusion equations which describe the time evolution of the bacterial density and the concentrations of the relevant chemical fields. This idea has been pursued by a number of groups. Here we present an additional model which specifically includes an evolution equation for the lubricant excreted by the bacteria. We show that when the diffusion of the fluid is governed by nonlinear diffusion coefficient branching patterns evolves. We study the effect of the rates of emission and decomposition of the lubricant fluid on the observed patterns. The results are compared with experimental observations. We also include fields of chemotactic agents and food chemotaxis and conclude that these features are needed in order to explain the observations.

cond-mat↗

arXiv1998

Continuous and discrete models of cooperation in complex bacterial colonies

We study the effect of discreteness on various models for patterning in bacterial colonies. In a bacterial colony with branching pattern, there are discrete entities - bacteria - which are only two orders of magnitude smaller than the elements of the macroscopic pattern. We present two types of models. The first is the Communicating Walkers model, a hybrid model composed of both continuous fields and discrete entities - walkers, which are coarse-graining of the bacteria. Models of the second type are systems of reaction diffusion equations, where the branching of the pattern is due to non-constant diffusion coefficient of the bacterial field. The diffusion coefficient represents the effect of self-generated lubrication fluid on the bacterial movement. We implement the discreteness of the biological system by introducing a cutoff in the growth term at low bacterial densities. We demonstrate that the cutoff does not improve the models in any way. Its only effect is to decrease the effective surface tension of the front, making it more sensitive to anisotropy. We compare the models by introducing food chemotaxis and repulsive chemotactic signaling into the models. We find that the growth dynamics of the Communication Walkers model and the growth dynamics of the Non-Linear diffusion model are affected in the same manner. From such similarities and from the insensitivity of the Communication Walkers model to implicit anisotropy we conclude that the increased discreteness, introduced be the coarse-graining of the walkers, is small enough to be neglected.

cond-mat.dis-nn↗

arXiv1998

Studies of Bacterial Branching Growth using Reaction-Diffusion Models for Colonial Development

Various bacterial strains exhibit colonial branching patterns during growth on poor substrates. These patterns reflect bacterial cooperative self-organization and cybernetic processes of communication, regulation and control employed during colonial development. One method of modeling is the continuous, or coupled reaction-diffusion approach, in which continuous time evolution equations describe the bacterial density and the concentration of the relevant chemical fields. In the context of branching growth, this idea has been pursued by a number of groups. We present an additional model which includes a lubrication fluid excreted by the bacteria. We also add fields of chemotactic agents to the other models. We then present a critique of this whole enterprise with focus on the models' potential for revealing new biological features.

cond-mat↗

arXiv1997

Two-Dimensional Polymers with Random Short-Range Interactions

We use complete enumeration and Monte Carlo techniques to study two-dimensional self-avoiding polymer chains with quenched ``charges'' $\pm 1$. The interaction of charges at neighboring lattice sites is described by $q_i q_j$. We find that a polymer undergoes a collapse transition at a temperature $T_θ$, which decreases with increasing imbalance between charges. At the transition point, the dependence of the radius of gyration of the polymer on the number of monomers is characterized by an exponent $ν_θ = 0.60 \pm 0.02$, which is slightly larger than the similar exponent for homopolymers. We find no evidence of freezing at low temperatures.

cond-mat.soft↗