Biology subjects

Nielsen, B. F.

Publications and source records attributed to Nielsen, B. F..

4 recordsLinked to original sources

bioRxiv2024

Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve

The phylodynamic curve [1] conceptualizes how immunity shapes the rate of viral adaptation in a non-monotonic fashion, through its opposing effects on viral abundance and the strength of selection. However, concrete and quantitative model realizations of this influential concept are rare. Here, we present an analytic, stochastic framework in which a population-scale phylodynamic curve emerges dynamically, allowing us to address questions regarding the risk and timing of emergence of viral immune escape variants. We explore how pathogen- and population-specific parameters such as strength of immunity, transmissibility and antigenic constraints affect the phylodynamic curve, leading to distinct phylodynamic curves for different pathogens. Motivated by the COVID-19 pandemic, we probe the likely effects of non-pharmaceutical interventions (NPIs), and the lifting thereof, on the risk of viral escape variant emergence. Looking ahead, the framework has the potential to become a useful tool for probing how natural immunity, as well as choices in vaccine design and distribution and the implementation of NPIs affect the evolution of common viral pathogens.

ecology↗

bioRxiv2024

One Hundred Years of Influenza A Evolution

Leveraging the simplicity of raw nucleotide distances, we provide an intuitive window into the evolution of the human influenza A nonstructural (NS) gene. In an analysis suggested by the eminent Danish biologist Freddy B. Christiansen, we illustrate the existence of a continuous genetic "backbone" of influenza A NS genes, steadily increasing in distance to the 1918 root over more than a century. Interestingly, the 2009 influenza pandemic represents a clear departure from this enduring genetic backbone. Utilizing nucleotide distance maps and phylogenetic analyses, we illustrate remaining uncertainties regarding the origin of the 2009 pandemic, highlighting the complexity of influenza evolution. The NS gene is interesting precisely because it experiences neutral genetic drift over long periods of time time, while sudden deviations from this drift pattern can indicate changes in other genes via the hitchhiking effect. Our approach employs two measures based on genotypic distance -- the rooted temporal Hamming map and the unrooted temporal Hamming distribution -- to analyze the evolutionary dynamics of the NS gene. The rooted Hamming map elucidates distances between a reference sequence and all other sequences over time. In contrast, the unrooted temporal Hamming distribution captures the distribution of genotypic distances between simultaneously circulating viruses, thereby revealing patterns of sequence diversity and epi-evolutionary dynamics. Our study aims to supplement traditional tree-based phylogenetic inference with these direct temporal distance-based measures, offering transparent insights into the evolution of the influenza NS gene.

evolutionary 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↗

bioRxiv2019

Model to link cell shape and polarity with organogenesis

How do tubes -- gut or neural tube -- form from flat sheets of polarized cells? The prevalent view is that it is a two-step process: first cells wedge to bend the sheet, then cells intercalate and extend the initial invagination into a tube. We computationally challenged this model by asking if one mechanism (either cell wedging or intercalation) may suffice for the entire sheet-to-tube transition. Using a physical model with epithelial cells represented by polarized point particles, we show that either cell intercalation or wedging alone can be sufficient and each can both bend the sheet and extend the tube. When working in parallel, the two mechanisms increase the robustness of the tube formation. The successful simulations of Drosophila salivary gland, Sea urchin gastrulation and mammalian neurulation support the generality of our results.

developmental biology↗