Biology subjects

König, B.

Publications and source records attributed to König, B..

8 recordsLinked to original sources

bioRxiv2026

Cytosolic factors govern vimentin network architecture and mechanics

Vimentin intermediate filaments are key cytoskeletal components forming networks with architectures distinct from other intermediate filament types, enabling specialized functions. Although assembly of individual filaments from soluble subunits is well characterized, dissecting how vimentin networks are organized has been challenging, as existing in vitro systems do not mimic the structures observed in cells. Thus, how cells establish higher-order vimentin organization remains unclear. Here, we reconstitute cell-like vimentin networks in vitro, using purified vimentin and extracts from mammalian and non-mammalian cells. Systematic variation of parameters reveals that cytosolic biomolecules, rather than intrinsic filament properties or generic ionic components, are the primary determinants of network architecture and mechanical behaviour. Importantly, network architecture is not universal but varies strongly according to the cell type from which the extract is derived, indicating that vimentin assemblies are tailored in a cell type-specific manner. Thus, this extract-based reconstitution system enables mechanistic dissection of intermediate filament regulation under near-native biochemical conditions, bridging the current gap between purified systems and the cellular environment. Our findings show that vimentin architecture and mechanics emerge primarily from cytosolic biomolecular factors that organize filaments into cell type-specific networks. These results establish cytosolic regulation as a central mechanism specifying intermediate filament network architecture and function.

cell biology↗

bioRxiv2025

Kinesin-induced buckling reveals the limits of microtubule self-repair

Microtubules are stiff cytoskeletal polymers whose ability to rapidly switch between growth and disassembly relies on a metastable lattice. This metastability is also reflected in their sensitivity to environmental conditions and in intrinsic lattice dynamics, where spontaneous tubulin loss is balanced by tubulin incorporation from solution - a process that also enables microtubules to self-repair when damaged. Whether such intrinsic self-repair is sufficient to preserve microtubule integrity during dynamic molecular-motor induced buckling, which frequently occurs in cells, remains unclear. Here, we show that kinesin-driven microtubule buckling in vitro induces severe lattice damage, leading to extensive tubulin incorporation. In many cases, however, the damage exceeds the microtubules capacity for self-repair, resulting in breakage. In contrast, microtubules survive continuous buckling substantially longer in the presence of intracellular factors. Our results identify the limits of intrinsic microtubule self-repair and demonstrate that additional cellular mechanisms are essential to maintain microtubule integrity under sustained mechanical load.

biophysics↗

bioRxiv2024

Vocal communication is seasonal in social groups of wild, free-living house mice

House mice (Mus musculus domesticus) are among the most widely studied laboratory models of mammalian social behavior, yet we know relatively little about the ecology of their behaviors in natural environments. Here, we address this gap using radiotelemetry to track social interactions in a population of wild mice over 10 years, from 2013 to 2023, and interpret these interactions in the context of passive acoustic monitoring data collected from August 2022 until November 2023. Using deep convolutional neural networks, we identify 1.3 million individual vocalizations and align them in time with continuously collected telemetry data recording social interactions between individually identifiable mice. We find that vocalization is seasonal and correlated with long-term dynamics in features of social groups. In addition, we find that vocalization is closely associated in time with entrances to and exits from those groups, occurs most often in the presence of pups, and is correlated with how much time pairs of mice spend together. This work identifies seasonal patterns in the vocalizations of wild mice and lays a foundation to investigate the social role of acoustic communication in wild populations of a classic laboratory model organism.

animal behavior and cognition↗

bioRxiv2021

Parent-offspring inference in highly inbred populations

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obfuscate genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human datasets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called SPORE (Specific Parent-Offspring Relationship Estimation). SPORE is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. SPORE therefore fills an important void in the arsenal of pedigree inference tools. Author SummaryKnowing the genealogical relationships among individuals is critical for genetic analyses, such as for identifying the mutations that cause diseases or that contribute to valuable agricultural traits such as milk production. Although many tools exist for establishing pedigrees using genetic information, these tools fail when individuals are highly inbred, such as in domesticated animals, or in groups of people in which consanguineous matings are common. Furthermore, existing tools do not work well when genetic information has errors at levels observed in modern datasets. Here, we present a novel approach to solve these problems. Our method is significantly more accurate than existing tools and more tolerant of errors in the genetic data. We expect that our method, which is simple to use and computationally efficient, will be a useful tool in a diversity of settings, from the studies of human and natural populations, to agricultural and experimental settings.

genetics↗

bioRxiv2021

Context-aware genomic surveillance reveals hidden transmission of a carbapenemase-producing Klebsiella pneumoniae

Genomic surveillance can inform effective public health responses to pathogen outbreaks. However, integration of non-local data is rarely done. We investigate two large hospital outbreaks of a carbapenemase-carrying Klebsiella pneumoniae strain in Germany and show the value of contextual data. By screening more than ten thousand genomes, 500 thousand metagenomes, and two culture collections using in silico and in vitro methods, we identify a total of 415 closely related genomes reported in 28 studies. We identify the relationship between the two outbreaks through time-dated phylogeny, including their respective origin. One of the outbreaks presents extensive hidden transmission, with descendant isolates only identified in other studies. We then leverage the genome collection from this meta-analysis to identify genes under positive selection. We thereby identify an inner membrane transporter (ynjC) with a putative role in colistin resistance. Contextual data from other sources can thus enhance local genomic surveillance at multiple levels and should be integrated by default when available.

microbiology↗

bioRxiv2021

Family dynamics reveal that female house mice preferentially breed in their maternal community

Whether females breed in their natal group is an important factor in the evolution of extended families in animal sociality. Breeding in natal groups comes with clear costs and benefits, depending on size of the group and presence of older relatives, including mothers. Studying individual decisions about whether to stay or leave can provide insight into the mechanisms and trade-offs governing the formation and structure of family groups. We investigated the family dynamics of a large population of free-ranging commensal house mice. Using dynamic community detection on long term datasets, we determined which females first bred in their natal group. We then looked at how this influenced breeding success. We found most females (77%) exhibited strong philopatry, breeding in their natal groups. Whether a female bred elsewhere was only predictable when natal groups were extremely small and related or large and unrelated. Despite this preference, breeding elsewhere made no difference in how quickly and successfully a female bred. However, presence of their mother did lead females to breed sooner when born during high breeding activity, when competition over reproduction is high. Based on these results, potential loss of fitness does not seem to be the main driver of philopatry in female house mice. The effect of the presence of mothers may indicate retaining prior social connections is an important benefit of breeding in the natal group. Mothers providing benefits also suggests lack of conflict between generations, which is likely an important attribute in the development of extended family groups. Lay summaryWhether animals breed in the group they are born in influences how they form extended family groups. Whether females stay will depend on properties such as presence of older relatives, including mothers. Using long-term wild mouse data, we track groups and which group females bred in. Most stayed, but leaving didnt reduce breeding success. Presence of mother, who generally stayed, did lead to earlier breeding. This might be a key advantage to remaining to breed.

animal behavior and cognition↗

bioRxiv2021

Targeted sensors for glutamatergic neurotransmission

Optical report of neurotransmitter release allows visualization of excitatory synaptic transmission. Sensitive genetically-encoded glutamate reporters operating with a range of affinities and emission wavelengths are available. However, without targeting to synapses, the specificity of the fluorescent signal is uncertain, compared to sensors directed at vesicles or other synaptic markers. We fused the state-of-the-art reporter iGluSnFR to glutamate receptor auxiliary proteins in order to target it to postsynaptic sites. Chimeras of Stargazin and gamma-8 that we named SnFR-{gamma}2 and SnFR-{gamma}8, retained function and reported spontaneous glutamate release in hippocampal cells, with apparently diffraction-limited spatial precision. In autaptic neurons on micro island cultures, evoked release could be quantitatively detected at tens of synapses in a field of view whilst evoked currents were recorded simultaneously. These experiments revealed a specific postsynaptic deficit from Stargazin overexpression, resulting in synapses with normal release but without postsynaptic responses. This defect was reverted by delaying overexpression. By working at different calcium concentrations, we determined that SnFR-{gamma}2 is a linear reporter of the global quantal parameters and short term synaptic plasticity, whereas iGluSnFR is not. On average, half of iGluSnFR regions of interest showing evoked fluorescence changes had intense rundown, whereas less than 5% of SnFR-{gamma}2 ROIs did. We provide an open-source analysis suite for extracting quantal parameters including release probability from fluorescence time series of individual and grouped synaptic responses. Taken together, postsynaptic targeting improves several properties of iGluSnFR and further demonstrates the importance of subcellular targeting for optogenetic actuators and reporters.

neuroscience↗

bioRxiv2020

Quantifying the influence of space on social group structure

When studying social behaviour, it can be important to determine whether the behaviour being recorded is actually driven by the social preferences of individuals. Many studies of animal social networks therefore attempt to disentangle social preferences from spatial preferences or restrictions. As such, there are a large number of techniques with which to test whether results from network analysis can be explained by random interactions, or interactions driven by similarities in space use. Selecting which of these methods to use will require determining to what extent space might influence social structure. Here we present a simple method (Social Spatial Community Assignment Test) to quantify the similarity between social and spatial group structure. We then apply this method to both simulated and empirical data of social interactions to demonstrate that it can successfully tease apart social and spatial explanations for groups. We first show that it can resolve the relative importance of space and social preferences in three simulated datasets in which interaction patterns are driven purely by space use, purely by social preferences or a mixture of the two. We then apply it to empirical data from a long-term study of free-ranging house mice. We find that while social structure is similar to spatial structure, there is still evidence for individuals possessing social preferences, with the importance of these preferences fluctuating between seasons. Our method provides a robust way of assessing the overlap between spatial and social structure, which will be invaluable to researchers when investigating the underlying drivers of social structure in wild populations.

animal behavior and cognition↗