Biology subjects

Sieber, M.

Publications and source records attributed to Sieber, M..

12 recordsLinked to original sources

bioRxiv2026

Do higher-order moments improve inference of population dynamics?

Fitting mathematical models of population dynamics to microbial time-series data allows us to estimate the ecological processes and interactions taking place in the microbiome. Repeated experiments of microbial systems yield replicates which slightly differ from each other. Some of this variability arises due to the fact that births and deaths occur at random. Most prior work focuses on fitting a deterministic mathematical model to the average across replicates. We use a stochastic model to fit the variability to the observed variability across replicates. Using a simulation-driven approach, we study the conditions under which our approach allows us to infer a larger fraction of ecological parameters correctly. We observe a substantial improvement in parameter inference. Lastly, our Bayesian approach not only allows us to incorporate prior information about the system, but also provides a distribution of parameters which conveys some idea of the uncertainty of the estimates.

ecology↗

bioRxiv2025

Single capsid mutations modulating phage adsorption, persistence, and plaque morphology shape evolutionary trajectories in {Phi}X174

The evolutionary success of lytic bacteriophages depends on key life-history traits, including adsorption, lysis time, burst size, and persistence in the environment. However, how these traits evolve to allow adaptation to different environments remains poorly understood. Here, we explored this question in {Phi}X174, combining experimental evolution and mathematical modelling. By investigating how serial transfer conditions shape evolutionary outcomes in liquid culture, we found that the time between transfers imposes divergent selection on adsorption and context-dependent directional selection on persistence. Longer transfer intervals, which allow multiple infection cycles until host depletion, favoured fast-adsorbing, highly persistent mutants that could rapidly initiate infections and remained viable in the absence of the host. In contrast, shorter transfer intervals selected for slower adsorption without substantially altering persistence. Mathematical modelling of phage population dynamics predicted that adsorption evolution during short transfers reflects a trade-off between two opposing selective forces within each transfer: an early phase in which susceptible hosts are abundant and adsorption is productive, favouring fast adsorption, and a later phase in which most hosts are already infected and adsorption primarily removes phage particles via attachment to already infected cells, favouring slower adsorption. A single-point mutation in the major capsid protein was sufficient to drive these changes in adsorption. In the case of fast-adsorbing mutants, this mutation was positively pleiotropic and also enhanced environmental persistence. Our findings show how simple changes in propagation conditions can steer phage phenotypes, providing insights relevant to evolutionary biology and phage therapy.

evolutionary biology↗

bioRxiv2023

Gut-associated functions are favored during microbiome assembly across C. elegans life

The microbiome expresses a variety of functions that influence host biology. The range of functions depends on composition of the microbiome, which itself can change during the lifetime of the host as a consequence of neutral assembly processes, host-mediated selection, and/or environmental conditions. To date, the exact dynamics of microbiome assembly, the underlying determinants as well as the resulting effects on host-associated functions are not always well understood. Here, we used the nematode Caenorhabditis elegans and a defined community of fully sequenced, naturally associated bacteria to study microbiome dynamics and functions across the lifetime of individual hosts under controlled experimental conditions. By applying the neutral and null models, we demonstrate that bacterial community composition initially shows strongly declining levels of stochasticity, which, however, increase during late worm life, suggesting the action of random assembly processes in aged hosts following first colonization of C. elegans. The adult microbiome is enriched in strains of the genera Ochrobactrum and Enterobacter in comparison to the direct substrate and a host-free control environment. Using pathway analysis, metabolic, and ecological modelling, we further found that the lifetime assembly dynamics lead to an increase in gut-associated functions in the host-associated microbiome, possibly indicating that the initially colonizing bacteria are beneficial for the worm. Overall, our study introduces a framework for studying microbiome assembly dynamics based on the stochastic models and inference of functions, yielding new insights into the processes determining host-associated microbiome composition and function. ImportanceThe microbiome plays a crucial role in host biology, with its functions depending on microbiome composition that can change during a hosts lifetime. To date, the dynamics of microbiome assembly and the resulting functions are not well understood. This study introduces a new approach to characterize the functional consequences of microbiome assembly by modelling both, the relevance of stochastic processes and metabolic characteristics of microbial community changes. The approach was applied to experimental time series data, obtained for the microbiome of the nematode Caenorhabditis elegans. The results revealed significant differences in host-associated and environmental microbiomes. Stochastic processes only played a minor role, and the host showed an increase in beneficial bacteria and an enrichment of gut-associated functions, possibly indicating that the host actively shapes composition of its microbiome. Overall, this study provides a framework for studying microbiome assembly dynamics and yields new insights into C. elegans microbiome functions.

evolutionary biology↗

bioRxiv2022

SUB-OPTIMAL ENVIRONMENTAL CONDITIONS PROLONG PHAGE EPIDEMICS IN BACTERIAL POPULATIONS

Infections by filamentous phages influence bacterial fitness in various ways. While phage-encoded accessory genes, e.g., virulence genes, can be highly beneficial, the production of viral particles is energetically costly and often reduces bacterial growth. Consequently, if costs outweigh benefits, bacteria evolve resistance which can shorten phage epidemics. Abiotic conditions are known to influence the net-fitness effect for infected bacteria. Their impact on the dynamics and trajectories of host resistance evolution, however, remains yet unknown. To address this, we experimentally evolved the bacterium Vibrio alginolyticus in the presence of a filamentous phage at three different salinity levels, i.e., (1) ambient (2) 50% reduction, and (3) fluctuations between reduced and ambient. In all three salinities, bacteria rapidly acquired resistance through super infection exclusion (SIE), whereby phage-infected cells acquired immunity at the cost of reduced growth. Over time, SIE was gradually replaced by evolutionary fitter surface receptor mutants (SRM). This replacement was significantly faster at ambient and fluctuating conditions compared to the low saline environment. Our experimentally parameterized mathematical model explains that suboptimal environmental conditions, in which bacterial growth is slower, slow down phage resistance evolution ultimately prolonging phage epidemics. Our results imply that, if filamentous phages encode virulence genes, these may persist longer in bacterial populations at sub-optimal environmental conditions, which, in times of climate change, are becoming more frequent. Thus, our future ocean may favour the emergence of phage-born pathogenic bacteria, and impose a greater risk for disease outbreaks, impacting not only marine animals but also humans.

evolutionary biology↗

bioRxiv2021

On the effect of inheritance of microbes in commensal microbiomes

BackgroundOur current view of nature depicts a world where macroorganisms dwell in a landscape full of microbes. Some of these microbes not only transit but establish themselves in or on hosts. Although hosts might be occupied by microbes for most of their lives, a microbe-free stage during their prenatal development seems to be the rule for many hosts. The questions of who the first colonizers of a newborn host are and to what extent these are obtained from the parents follow naturally. ResultsWe have developed a mathematical model to study the effect of the transfer of microbes from parents to offspring. Even without selection, we observe that microbial inheritance is particularly effective in modifying the microbiome of hosts with a short lifespan or limited colonization from the environment, for example by favouring the acquisition of rare microbes. ConclusionBy modelling the inheritance of commensal microbes to newborns, our results suggest that, in an eco-evolutionary context, the impact of microbial inheritance is of particular importance for some specific life histories.

ecology↗

bioRxiv2021

The effect of microbial selection on the occurrence-abundance patterns of microbiomes

Theoretical models are useful to investigate the drivers of community dynamics. Notable are models that consider the events of death, birth, and immigration of individuals assuming they only depend on their abundance - thus, all types share the same parameters. The community level expectations arising from these simple models and their agreement to empirical data have been discussed extensively, often suggesting that in nature, rates might indeed be neutral or their differences not important. But, how robust are these model predictions to type-specific rates? And, what are the consequences at the level of types? Here, we address these questions moving from simple to diverse communities. For this, we build a model where types are differently adapted to the environment. We adapt a computational method from the literature to compute equilibrium distributions of the abundance. Then, we look into the occurrence-abundance pattern often reported in microbial communities. We observe that large immigration and biodiversity - common in microbial systems - lead to such patterns, regardless of whether the rates are neutral or non-neutral. We conclude by discussing the implications to interpret and test empirical data.

ecology↗

bioRxiv2020

Measuring the quality of scientific references in Wikipedia: an analysis of more than 80M citations to over 800,000 scientific articles

Wikipedia is a widely used online reference work which cites hundreds of thousands of scientific articles across its entries. The quality of these citations has not been previously measured, and such measurements have a bearing on the reliability and quality of the scientific portions of this reference work. Using a novel technique, a massive database of qualitatively described citations, and machine learning algorithms, we analyzed 1,923,575 Wikipedia articles which cited a total of 841,821 scientific articles, and found that most cited articles (58%) are uncited or untested by subsequent studies, while the remainder show a wide variability in contradicting or supporting evidence (2-40%).View Full Text

scientific communication and education↗

bioRxiv2019

Bacteriophage can promote the emergence of physiologically sub-optimal host phenotypes

Reproduction of bacteria-specific viruses, or bacteriophage, requires the replication and translation machinery of the host cell. As a consequence, phage fitness depends intimately on the physiological state, i.e. growth rate, of the host. We include this dependence of critical phage traits on host growth rate in a mathematical model of a bacteria-phage interaction. This leads to a feedback loop between phage success, host population size, nutrient availability and host growth rate. We find that this feedback allows slow growing bacteria to have a competitive advantage in the presence of phage. Under certain conditions a slow growing host mutant can even drive the phage to extinction. Since in a phage-free environment slow growth is deleterious, the mutant subsequentely dies out as well, constituting a kind of altruistic scenario similar to abortive infections.

ecology↗

bioRxiv2018

The Neutral Metaorganism

Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota. The hosts often pose highly selective environments, which only a subset of the environmentally available microbes are able to colonize. From the hosts perspective it seems useful to shape the community composition of these allowed microbes to promote a beneficial host-microbe symbiosis. In contrast to this, neutral models assume that the structure of the microbiota is entirely shaped by random population dynamics and dispersal. We here show that microbiota community structure from a wide range of host organisms, in particular including previously understudied invertebrates, is in almost all cases consistent with neutral expectations. Moreover, we demonstrate that apparent discrepancies with the neutral model can be due to transient community states rather than host selection. In conclusion, even though hosts are often assumed to control microbiota composition to ensure beneficial interactions, our broad-scale analysis highlights that following colonization, it could rather be neutral processes that determine microbial community structure.

ecology↗

bioRxiv2018

Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism in Drosophila

Tissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with developmental pathways. Using the Drosophila midgut as a model we found that during the first four days of adult life, dietary lipids including cholesterol, determine how many enteroendocrine (ee) cells differentiate and persist in the posterior midgut where lipids are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, and utilization, is required for sterol-mediated changes in ee number. Dietary cholesterol influences new intestinal epithelial cell differentiation from stem cells by altering the level and persistance of Notch signaling. Exogenous lipids modulate signaling by changing the stability of the Delta ligand and Notch intracellular domain and their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues such as the ovary, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in ee number in young animals contribute to a metabolic program adapted to the prevailing nutrient environment that persists after the diet changes. A low sterol diet also slows the proliferation of enteroendocrine tumors initiated by disruptions in the Notch pathway. These studies show that a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.

developmental biology↗

bioRxiv2018

One man’s trash is another man’s treasure - the effect of bacteria on phytoplankton-zooplankton interactions in chemostat systems

Chemostat experiments are employed to study predator-prey and other trophic interactions, frequently using phytoplankton-zooplankton systems. These experiments often use population dynamics as fingerprints of ecological and evolutionary processes, assuming that the contributions of all major actors to these dynamics are known. However, bacteria are often neglected although they are frequently present. We argue that even without external carbon sources bacteria may affect the experimental outcomes depending on experimental conditions and the physiological traits of bacteria, phytoplankton and zooplankton. Using a static carbon flux model and a dynamic simulation model we predict the minimum and maximum impact of bacteria on phytoplankton-zooplankton population dynamics. Under bacteria-suppressing conditions, we find that the effect of bacteria is indeed negligible and their omission justified. Under bacteria-favouring conditions, however, bacteria may strongly affect average biomasses. Furthermore, the population dynamics may become highly complex resulting in wrong conclusions if bacteria are not considered. Our model results provide suggestions to reduce the bacterial impact experimentally. Next to optimizing experimental conditions (e.g. the dilution rate) the appropriate choice of the zooplankton predator is decisive. Counterintuitively, bacteria have a larger impact if they are not ingested by the predator as high bacterial biomasses and complex population dynamics arise via competition for nutrients with the phytoplankton. Only if the predator is at least partly bacterivorous the impact of bacteria is minimized. Our results help to improve both the design of chemostat experiments and their interpretation and thus advance the study of ecological and evolutionary processes in aquatic food webs.

ecology↗

bioRxiv2017

Temperate phages as frequency-dependent weapons in bacterial competition

Microbial communities are accompanied by a diverse array of viruses. Through infections of abundant microbes, these viruses have the potential to mediate competition within the community, effectively weakening competitive interactions and promoting coexistence. This is of particular relevance for host-associated microbial communities, since the diversity of the microbiota has been linked to host health and functioning. Here, we study the interaction between two key members of the microbiota of the freshwater metazoan Hydra vulgaris. The two commensal bacteria Curvibacter sp. and Duganella sp. protect their host from fungal infections, but only if both of them are present. Coexistence of the two bacteria is thus beneficial for Hydra. Intriguingly, Duganella sp. appears to be the superior competitor in vitro due to its higher growth rate when both bacteria are grown seperately, but in coculture the outcome of competition depends on the relative initial abundances of the two species. The presence of an inducible prophage in the Curvibacter sp. genome which is able to lytically infect Duganella sp., led us to hypothesise that the phage modulates the interaction between these two key members of the Hydra microbiota. Using a mathematical model we show that the interplay of the lysogenic life-cycle of the Curvibacter phage and the lytic life-cycle on Duganella sp. can explain the observed complex competitive interaction between the two bacteria. Our results highlight the importance of taking lysogeny into account for understanding microbe-virus interactions and show the complex role phages can play in promoting coexistence of their bacterial hosts.

microbiology↗