Biology subjects

Philipp, L.

Publications and source records attributed to Philipp, L..

3 recordsLinked to original sources

bioRxiv2025

3D Reconstruction of Dinoflagellate Chromosomes from Hi-C Data Refutes the Cholesteric Liquid Crystal Hypothesis

Dinoflagellates have permanently condensed chromosomes that are often described as liquid crystalline. Specifically, a Cholesteric Liquid Crystal (CLC) model was proposed in which DNA is organized into parallel fibers within stacked discs, such that the fiber orientation rotates by a constant angle between adjacent discs. Extrachromosomal loops extending from the discs were hypothesized to be more accessible and thus to contain transcriptionally active genes. Although the CLC model captures some features of dinoflagellate chromosome structure, its validity has not been rigorously tested against modern genomic data. Here, we use chromatin conformation capture (Hi-C) data to simulate 3D conformations of chromosome scaffolds for three dinoflagellate species: Fugacium kawagutii, Symbiodinium microadriaticum, and Breviolum minutum. Consensus and population-based modeling generate diverse polymer conformations with moderate orientational and nematic order. However, we find no evidence of cholesteric discs. Moreover, contact probability curves from empirical Hi-C data are inconsistent with the CLC model. Nevertheless, we show that introducing locus-specific boundaries into the CLC model can produce simulated Hi-C contact maps with topologically associating domains (TADs), which are observed in experimental Hi-C contact maps for these species. Finally, by mapping RNA-seq data onto our simulated conformations, we show that actively transcribed genes are present throughout entire chromosomes, and not exclusively on extrachromosomal loops or at the surface. Our results challenge the long-standing CLC model and suggest that dinoflagellate chromosomes are organized into condensed but non-crystalline structures that do not impede transcription.

biophysics↗

bioRxiv2024

Bacterial transcriptional repressor NrdR - a flexiblemultifactorial nucleotide sensor

NrdR is a bacterial transcriptional repressor consisting of a Zn-ribbon domain followed by an ATP-cone domain. Understanding its mechanism of action could aid the design of novel antibacterials. NrdR binds specifically to two "NrdR boxes" upstream of ribonucleotide reductase operons, of which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, where we identified a new box. We show that E. coli NrdR (EcoNrdR) has similar binding strength to all three sites when loaded with ATP plus dATP or equivalent diphosphate combinations. No other combination of nucleotides promotes binding to DNA. We present crystal structures of EcoNrdR-ATP-dATP and EcoNrdR-ADP-dATP, which are the first high-resolution crystal structures of an NrdR. We have also determined cryo-EM structures of DNA-bound EcoNrdR-ATP-dATP and novel filaments of EcoNrdR-ATP. Tetrameric forms of EcoNrdR involve alternating interactions between pairs of Zn-ribbon domains and ATP-cones. The structures reveal considerable flexibility in relative orientation of ATP-cones vs Zn-ribbon domains. The structure of DNA-bound EcoNrdR-ATP-dATP shows that significant conformational rearrangements between ATP-cones and Zn-ribbons accompany DNA binding while the ATP-cones retain the same relative orientation. In contrast, ATP-loaded EcoNrdR filaments show rearrangements of the ATP-cone pairs and sequester the DNA-binding residues of NrdR such that they are unable to bind to DNA. Our results, in combination with a previous structural and biochemical study, point to highly flexible EcoNrdR structures that when loaded with the correct nucleotides adapt to an optimal promoter binding conformation.

biophysics↗

bioRxiv2024

Habitat isolation diminishes potential of self-organised pattern formation to promote local diversity in metacommunities

Progressive destruction and isolation of natural habitat is a major threat to biodiversity worldwide. In this study we use a trophic metacommunity model with complex, spatially explicit structure to address how the interaction of local and regional processes affects the functional diversity of autotroph (producer) communities within and between individual habitat patches. One important driver of biodiversity in metacommunities is spatial heterogeneity of the environment, as it enables source-sink dynamics between patches. Besides a-priori differences in the environmental conditions, heterogeneous distributions of resources and species biomasses can also emerge through self-organised pattern formation caused by scale-dependent feedback between local trophic and regional dispersal dynamics. We show that this emergent heterogeneity can enhance the functional diversity of local autotroph communities by jointly strengthening source-sink dynamics and reducing stabilising selection pressure. Our results indicate that this effect is particularly strong in highly connected metacommunities, while metacommunity size (number of patches) alone plays a lesser role. We demonstrate that the positive effect on local diversity is driven by an eco-evo-spatial feedback loop that is fueled by the asynchronous biomass- and trait dynamics between the patches created by self-organised pattern formation. In highly connected metacommunities, oscillatory biomass patterns with particularly large amplitude strengthen this feedback loop. Our findings are highly relevant in the light of anthropogenic habitat changes that often destroy dispersal pathways, thereby increasing habitat isolation, lowering overall connectance of metacommunities and ultimately threatening the biodiversity in local habitats. Only a joint investigation of the contributing ecological, evolutionary, and spatial mechanisms in complex model systems can yield comprehensive understanding of these processes, allowing for the development of strategies to mitigate adverse anthropogenic influence.

ecology↗