Biology subjects

sneppen, k.

Publications and source records attributed to sneppen, k..

6 recordsLinked to original sources

bioRxiv2026

Long-range seeding drives exponential growth in early respiratory viral infection

Respiratory viruses spread within the host through both local expansion and occasional long-range dissemination that seeds new infection foci. We present LEAP, an analytically tractable within-host model that captures this two-scale process by coupling local plaque growth to long-range seeding. The model reduces to an age-dependent branching process and yields a closed-form expression for the exponential growth rate during early infection. Using empirical data to parametrize the model, we find that productive dissemination requires only a small number of successful long-range seeding events per infected cell, with distinct values for SARS-CoV-2 and influenza A virus. LEAP further predicts that, in these well-adapted viruses, interferon-mediated restriction only weakly affects exponential growth, while remaining decisive for poorly adapted ones. More broadly, the model provides a flexible framework for experimentally testable predictions of early infection dynamics. Significance StatementRespiratory viral infection is an inherently spatial process, in which the virus must colonize large areas of the airways to optimize reproduction. Recent studies in animal models infected with influenza A or SARS-CoV-2 have documented long-range stochastic jumps of viral populations between distant regions of the respiratory tract. The emerging picture is one of two co-occurring spatial processes: slow, local plaque expansion and long-range seeding events that are rare but crucial to rapid colonization of the airways. We introduce LEAP (Lotka-Euler Airway Pathogen model), a simple mathematical within-host model that captures these two-scale dynamics by coupling local plaque growth to stochastic long-range seeding. Using LEAP, measurements from the petri dish can directly produce predictions of infection dynamics in the body.

immunology↗

bioRxiv2024

δ-α cell-to-cell interactions modulate pancreatic islet Ca2+ oscillation modes

Glucose-induced pancreatic islet hormone release is tightly coupled with oscillations in cytoplasmic free Ca2+ concentration of islet cells, which is regulated by a complex interplay between intercellular and intracellular signaling. {delta} cells, which entangle with cells located at the islet periphery, are known to be important paracrine regulators. However, the role of {delta} cells in regulating Ca2+ oscillation pattern remains unclear. Here we show that {delta}- cell-to-cell interactions are the source of variability in glucose-induced Ca2+ oscillation pattern. Somatostatin secreted from {delta} cells prolonged the islets oscillation period in an cell mass-dependent manner. Pharmacological and optogenetic perturbations of {delta}- interactions led islets to switch between fast and slow Ca2+ oscillations. Continuous adjustment of {delta}- coupling strength caused the fast oscillating islets to transition to mixed and slow oscillations. We developed a mathematical model, demonstrating that the fast-mixed-slow oscillation transition is a Hopf bifurcation. Our findings provide a comprehensive understanding of how {delta} cells modulate islet Ca2+ dynamics and reveal the intrinsic heterogeneity of islets due to the structural composition of different cell types. HighlightsO_LISomatostatin slows down islet Ca2+ oscillations in an cell mass-dependent manner. C_LIO_LIPharmacological and optogenetic perturbations of {delta}- interaction cause islet Ca2+ oscillation mode switching. C_LIO_LIContinuous tuning of {delta}- interaction strength induces fast-mixed-slow oscillation transition successively. C_LIO_LIMathematical modeling shows the fast-mixed-slow oscillation transition as a Hopf bifurcation. C_LI

systems biology↗

bioRxiv2023

Self-inhibiting percolation and viral spreading in epithelial tissue

SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.

systems biology↗

bioRxiv2022

Theoretical analysis of confinement mechanisms for epigenetic modifications of nucleosomes

Nucleosomes and their modifications often facilitate gene regulation in eukaryotes. Certain genomic regions may obtain alternate epigenetic states through enzymatic reactions forming positive feedback between nucleosome states. How a system of nucleosome states maintains confinement is an open question. Here we explore a family of stochastic dynamic models with combinations of readwrite enzymes. We find that a larger number of intermediate nucleosome states increases both the robustness of linear spreading in models with only local recruitment processes and the degree of bi-stability under conditions with at least one non-local recruitment. Further, supplementing the positive feedback with one negative feedback acting over long distances along the genome enables effective confinement of epigenetic, bistable regions. Our study emphasizes the importance of determining whether each particular read-write enzyme acts only locally or between distant nucleosomes.

genomics↗

bioRxiv2020

Pancreatic α and β cells are globally phase-locked

The Ca2+ modulated pulsatile secretion of glucagon and insulin by pancreatic and {beta} cells plays a key role in glucose homeostasis. However, how and {beta} cells coordinate via paracrine interaction to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice in which and {beta} cells were labeled with different colors, we were able to record islet Ca2+ signals at single cell level for long times. Upon glucose stimulation, we observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a transient period, the oscillations of and {beta} cells were globally phase-locked, i.e., the two types of cells in an islet each oscillate synchronously but with a phase shift between the two. While the activation of cells displayed a fixed time delay of ~20 s to that of {beta} cells, {beta} cells activated with a tunable delay after the cells. As a result, the tunable phase shift between and {beta} cells set the islet oscillation period and pattern. Furthermore, we demonstrated that the phase shift can be modulated by glucagon. A mathematical model of islet Ca2+ oscillation taking into consideration of the paracrine interaction was constructed, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction to generate stable but tunable islet oscillation patterns.

systems biology↗

bioRxiv2019

Regime shifts in a phage-bacterial ecosystem and strategies for its control

The competition between bacteria often involves both nutrients and phage predators and may give rise to abrupt regime shifts between the alternative stable states characterized by different species compositions. While such transitions have been previously studied in the context of competition for nutrients, the case of phage-induced bistability between competing bacterial species has not been considered yet. Here we demonstrate a possibility of regime shifts in well-mixed phage-bacterial ecosystems. In one of the bistable states the fast-growing bacteria competitively exclude the slow-growing ones by depleting their common nutrient. Conversely, in the second state the slow-growing bacteria with a large burst size generate such a large phage population that the other species cannot survive. This type of bistability can be realized as the competition between a strain of bacteria protected from phage by abortive infection and another strain with partial resistance to phage. It is often desirable to reliably control the state of microbial ecosystems, yet bistability significantly complicates this task. We discuss successes and limitations of one control strategy in which one adds short pulses to populations of individual species. Our study proposes a new type of phage therapy, where introduction of the phage is supplemented by addition of a partially resistant host bacteria.\n\nIMPORTANCEPhage-microbial communities play an important role in human health as well as natural and industrial environments. Here we show that these communities can assume several alternative species compositions separated by abrupt regime shifts. Our model predicts these regime shifts in the competition between bacterial strains protected by two different phage defense mechanisms: abortive infection/CRISPR and partial resistance. The history dependence caused by regime shifts greatly complicates the task of manipulation and control of a community. We propose and study a successful control strategy via short population pulses aimed at inducing the desired regime shifts. In particular, we predict that a fast-growing pathogen could be eliminated by a combination of its phage and a slower-growing susceptible host.

microbiology↗