Biology subjects

Koenig, B.

Publications and source records attributed to Koenig, B..

7 recordsLinked to original sources

bioRxiv2025

MAP65-1/PRC1 reinforces microtubules through nucleation

Microtubules are dynamic cytoskeletal filaments that help shape cells and guide their response to external cues, including mechanical stress. How cells reorganize and reinforce microtubule arrays under stress remains poorly understood. Here, we show that MAP65-1/PRC1 promotes microtubule nucleation on pre-existing lattices in vitro, particularly on microtubules with lattice defects and damage sites associated with mechanical stress. MAP65-1 preferentially binds bent microtubules both in vitro and in cells, likely because bending induces lattice damage, enhancing nucleation on and bundling of these microtubules in vitro. This creates a potential feedback loop where mechanical stress promotes MAP65-1 binding, which in turn stabilizes microtubules by nucleation and bundling and reinforces the alignment of the array with mechanical stress. Thus, we reveal a previously unknown role for MAP65/PRC1 proteins in lattice-based nucleation and suggest a mechanism by which cells record and respond to mechanical stress through microtubule reorganization.

cell biology↗

bioRxiv2025

Expanding the Repertoire of Photoswitchable Unnatural Amino Acids for Enzyme Engineering

Photoswitchable unnatural amino acids (psUAAs) play a crucial role in the engineering of light-sensitivity in enzymes, which holds significant promise for diverse applications such as biotherapy and biocatalysis. Besides near-quantitative photoconversion, the success and expediency of a psUAA for a certain application is defined by its interaction potential with the enzyme, its thermal stability and its effective wavelength of irradiation. To establish high versatility in the current repertoire, we have designed and synthesized six psUAAs based on azobenzene, arylazopyrazole, arylazothiazole, hemithioindigo and spiropyran photoswitches. The resulting psUAAs exhibit an enhanced interaction potential within an enzyme owing to their capacity for hydrogen bonding, ionic interactions, and metal ion coordination. Moreover, we observed diverse photochemical behaviors among the psUAAs, with four of them reversibly switching between the isomers with purely visible light. Notably, we identified orthogonal aminoacyl-tRNA synthetases that facilitate the incorporation of five of the six psUAAs co-translationally and computationally analyzed the synthetase-psUAA interactions. Finally, we evaluated the photochemical behavior of the five psUAAs within an enzymatic model and tested the photocontrol of catalysis confirming their diversity. Ultimately, our findings significantly expanded the repertoire of psUAAs and demonstrated their feasibility for enzyme engineering studies.

synthetic biology↗

bioRxiv2024

Promoting enzyme catalysis via azobenzene facilitated vibrational energy transfer

Azobenzene is a widely recognized tool for achieving artificial spatiotemporal control of enzyme activity using light. Photocontrol reversibility is typically based on photostationary states with varying E and Z isomer compositions achieved through irradiation at specific wavelengths. Here, we report an alternative mechanism for azobenzene based enzyme regulation, discovered through simultaneous irradiation with two wavelengths. Using two engineered variants of imidazole glycerol phosphate synthase, in which azobenzene was incorporated as an unnatural amino acid to enable reversible control under monochromatic irradiation, we uncovered unique behavior under dichromatic irradiation. Notably, a distinct spectroscopic signal from the azobenzene moiety emerged during simultaneous irradiation at 365 nm and 420 nm and vanished upon return to the dark. Intriguingly, dichromatic irradiation triggered a reproducible two-fold increase in catalytic activity and an instantaneous return to baseline activity in the dark for one variant. In contrast, the other variant and the wild-type enzyme maintained their baseline activity under the same conditions. These findings reveal an unexplored avenue for azobenzene photoswitching, offering a novel approach to photocontrol with potential applications in sequentially regulating multiple enzymes, especially when combined with monochromatic irradiation strategies.

biophysics↗

bioRxiv2020

Population density and temperature influence the return on maternal investment in wild house mice

In mammals, reproduction is influenced by competitive stress, temperature and food availability and these factors might be crucial already during early life. Favourable early life environment and high maternal investment are expected to improve survival and reproduction. In mammals, maternal investment via lactation predicts offspring growth. As body mass is often associated with fitness consequences, females have the potential to influence offspring fitness through their level of investment, which might interact with effects of population density and temperature. Here, we investigate the relationship between pup body mass at day 13 (used as approximation for weaning mass) and individual reproductive parameters as well as longevity under natural variation in population density and temperatures. Further, we assess the extent to which mothers influence the body mass of their offspring until weaning. We analysed life data of 384 house mice (Mus musculus domesticus) from a free-living wild population that was not food limited. We found a complex effect of population density, temperature and maternal investment on life-history traits related to fitness: Shorter longevity with increasing pup body mass at day 13; delayed reproduction of heavier pups when raised at warmer temperatures; and increased lifetime reproductive success for heavier pups at high densities. House mice could use population density and temperature as cues for predicting future environmental conditions, allowing a mother to adjust her investment according to the environment in which offspring will breed in order to maximise fitness. This study highlights the importance of considering ecological conditions in combination with maternal effects.

evolutionary biology↗

bioRxiv2020

Contact patterns reveal a stable dynamic community structure with fission-fusion dynamics in wild house mice

Living in groups is a widely adopted strategy in gregarious species. For group-living individuals it is crucial to be capable to integrate into a social structure. While there is an intuitive understanding that the concept of a group arises through some form of cohesion between its members, the exact definition of what constitutes a group and thus tasks like the detection of the dynamics of a group over time is a challenge. One way of measuring cohesion is through direct interactions between individuals. However, there is increasing evidence that associations between individuals can be mediated by others, and thus, that the drivers for group cohesion extend beyond direct individual interactions. We use dynamic community detection, allowing to relate individuals beyond direct contacts, both structurally and temporally, to study the social structure in a long-term study of a population of free-ranging house mice in a barn in Switzerland. During the 2-year study period, mice had unlimited access to food, and population density increased by 50%. Despite strong fluctuations in individual contact behaviour, population demography and structure embed into long-lived dynamic communities that are characterised by spatial fidelity, persist over several seasons and reproduction cycles, and considerably extend the life-span of single individuals. Within these multi-male and multi-female communities, seasonal changes strongly affect their structure, leading to fission-fusion like dynamics. We identify female-female interactions as the main driver for the longevity of these communities, a finding that contrasts with prior reports of the importance of a dominant male for the stability of a group. Moreover, males have a drastically shorter presence time in the study population and more often move between communities than females. Nevertheless, interacting with other breeding males in stable communities increases the duration of male presence and thus, potentially, reproductive success. Our analysis of contact patterns in a rodent that uses shelters to rest, hide and rear offspring emphasises the importance of female-bonded communities in the structuring of the population.

ecology↗

bioRxiv2019

Distributed representations of protein domains and genomes and their compositionality

Learning algorithms have at their disposal an ever-growing number of metagenomes for biomining and the study of microbial functions. We propose a novel representation of function called nanotext that scales to very large data sets while capturing precise functional relationships.\n\nThese relationships are learned from a corpus of 32 thousand genome assemblies with 145 million protein domains. We treat the protein domains in a genome like words in a document, assuming that protein domains in a similar context have similar \"meaning\". This meaning can be distributed by the Word2Vec embedding algorithm over a vector of numbers. These vectors not only encode function but can be used to predict even complex genomic features and phenotypes.\n\nWe apply nanotext to data from the Tara ocean expedition to predict plausible culture media and growth temperatures for microorganisms from their metagenome assembled genomes (MAGs) alone. nanotext is freely released under a BSD licence (https://github.com/phiweger/nanotext).

genomics↗

bioRxiv2018

The Clinical Imperative for Inclusivity: Race, Ethnicity, and Ancestry (REA) in Genomics

The Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group highlights the need to develop guidance on race, ethnicity, and ancestry (REA) data collection and use in clinical genomics. We present quantitative and qualitative evidence to characterize: 1) acquisition of REA data via clinical laboratory requisition forms, and 2) information disparity across populations in the Genome Aggregation Database (gnomAD) at clinically relevant sites as determined by variants in ClinVar. Our requisition form analysis showed substantial heterogeneity in clinical laboratory ascertainment of REA, as well as marked incongruity among terms used to define REA categories. There was also striking disparity across REA populations in the amount of information available about variants at clinically relevant sites in gnomAD. European ancestral populations constituted the majority of observations (55.8%), allele counts (59.7%), and private alleles (56.1%) in gnomAD at 550 loci with \"pathogenic\" and \"likely pathogenic\" expert-reviewed variants in ClinVar. Our findings highlight the importance of implementing and supporting programs to increase diversity in genome sequencing and clinical genomics, as well as measuring uncertainty around population-level datasets that are used in variant interpretation. Finally, we suggest the need for a standardized REA data collection framework to be developed and adopted across clinical genomics.

genomics↗