Biology subjects

Cole, F.

Publications and source records attributed to Cole, F..

7 recordsLinked to original sources

bioRxiv2026

Nematode species differ in susceptibility and response to the nematode-trapping fungus Arthrobotrys oligospora

Fungal predators of nematodes are widespread and represent promising candidates for biological control of parasitic nematodes. However, the behavioural and molecular mechanisms underlying nematode-fungus interactions remain poorly understood, especially for nematodes other than Caenorhabditis elegans. We investigated the interactions between the nematode-trapping fungus Arthrobotrys oligospora and three nematode species: (i) free-living C. elegans, (ii) fig-associated C. inopinata, and (iii) the free-living adult life cycle stage of the gastrointestinal parasite Strongyloides ratti. A. oligospora trapped S. ratti more efficiently than either C. elegans or C. inopinata. Behavioural analyses revealed species-specific differences in nematode locomotion. S. ratti moved slower, travelled shorter distances and showed lower displacement than Caenorhabditis spp. To test whether locomotion influences fungal trapping, we examined eight C. elegans mutants with hyper- or hypoactive locomotory phenotypes. Although both groups moved at similar speeds, hyperactive mutants showed greater displacement, which positively correlated with trap formation but did not explain trapping efficiency by A. oligospora. We investigated the fungal response during interaction with the three nematodes. Exposure to S. ratti, but not to Caenorhabditis spp, resulted in reduced sporulation and differential expression of sporulation-associated genes. In nematodes, myosin-related genes responded to A. oligospora in a species-specific manner, including upregulation in C. elegans and downregulation in S. ratti. These transcriptional changes may reflect alterations in muscle structure, including reduction in dense body and mitochondrial size in Caenorhabditis species but not S. ratti during A. oligospora exposure. Together, our findings demonstrate that both fungal and nematode responses are nematode species dependent. These results improve our understanding of nematode-fungus interactions and highlight the importance of nematode species when developing nematode-trapping fungi as a biological control agent.

evolutionary biology↗

bioRxiv2026

ZCWPW1 organizes telomeric architecture to drive meiotic chromosome movements

Meiotic homolog pairing relies on programmed DNA recombination and large-scale chromosome movements, yet, how these genetic and mechanical events are coordinated remains unclear. ZCWPW1 is a histone reader that recognizes PRDM9-deposited chromatin marks. We identify an unexpected role for ZCWPW1 as a regulator of rapid prophase movements (RPMs). Using super-resolution imaging, we show that ZCWPW1 is strongly enriched at subtelomeric regions of mouse spermatocytes, where it stabilizes TRF1, LINC complex components, dynein, and meiosis-specific cohesin (STAG3). Loss of ZCWPW1 disrupts telomere architecture, weakens telomere-LINC- motor coupling, and abolishes chromosome movement, leading to defective synapsis and pairing, and persistence of DSBs. These defects are more severe than, and mechanistically independent of, those observed in Prdm9-/- spermatocytes. Together, our findings reveal that ZCWPW1 acts independently of PRDM9 as a chromatin-based intranuclear regulator of telomere architecture and telomere-led chromosome movements, thereby linking telomeric chromatin state to nuclear force transmission required for faithful meiotic progression. Significance StatementMeiotic pairing requires recombination and telomere-led chromosome movements, yet no chromatin factor has been shown to regulate both. We identify ZCWPW1 as the first chromatin-based regulator of rapid prophase movements. ZCWPW1 organizes telomeric chromatin and promotes cohesin and motor assembly at telomeres that for force transmission across the nuclear envelope. Loss of ZCWPW1 disrupts the telomere-nuclear envelope mechanical coupling, impairing motion and altering recombination. This function doesnt rely on PRDM9 despite their co-evolution and co-expression, challenging the prevailing view that ZCWPW1 only acts downstream of PRDM9 in DNA repair. Our findings show that chromatin readers can function as structural regulators of genome organization, revealing a conserved mechanism integrating chromosome structure, motion, and repair to ensure proper pairing and fertility.

cell biology↗

bioRxiv2025

Brownian DNA Computing

Conventional silicon computing is constrained by energy demands, limited parallelism, and poor compatibility with living systems, motivating the exploration of molecular alternatives. Here, we realize Brownian DNA computing, a hitherto theoretical framework, for energy efficient computation in which coupled molecular balances on a DNA origami scaffold form Brownian Logic Elements (BLEs) that harnesses thermal fluctuations for computation. By encoding multiple logic gates into a programmed energy landscape, these BLEs execute all fundamental Boolean logic gates, complex circuits such as half-adders, and multi-input operations, while also enabling non-Boolean logic with multi-valued outputs in a single compact gate. Computation arises through thermally driven exploration of a near-flat configurational energy landscape, without reliance on consumable fuel strands for cascading signal propagation, making the process fast, resettable, and compatible with operation near reversible thermodynamic limits. Transient-input protocols further allow the BLE energy landscape to be controlled quasistatically, providing a route toward reversible Brownian computation. In combination with single-molecule readout, Brownian DNA computing establishes a new foundation for molecular information processing with potential applications in biocomputing, soft robotics, and energy-efficient nanodevices.

biophysics↗

bioRxiv2025

Minimally Invasive DNA-Mediated Photostabilization for Extended Single-Molecule and Super-resolution Imaging

Photobleaching of fluorescence labels poses a major limitation in single-molecule and super-resolution microscopy. Conventional photostabilization methods, such as oxygen removal and addition of high concentrations of photostabilization additives, often require careful fluorophore selection and can disrupt the biological environment. To address these limitations, we developed a modular and minimally invasive photostabilization approach that utilizes DNA-mediated delivery of a photostabilizer directly to the imaging site. Under lower excitation intensities, the DNA-mediated strategy outperformed solution-based approaches, achieving efficient photostabilization at significantly lower additive concentrations. However, at higher excitation intensities, the stability of a single photostabilizer molecule became the limiting factor. To overcome this and reduce the loss of localizations in DNA-PAINT experiments we have also implemented a recovery scheme where the photostabilizer is continuously replenished at the imaging site. We further extended the approach to cell imaging, demonstrating improved localization rate and precision in 3D-DNA PAINT measurements. DNA-mediated photostabilization offers a promising solution for imaging applications where high additive concentrations are prohibited. Its modularity enables adaptation to various imaging schemes and ultimately expands the repertoire of fluorophores suitable for single-molecule and super-resolution imaging.

biophysics↗

bioRxiv2024

Spring-loaded DNA origami arrays as energy-supplied hardware for modular nanorobots

DNA origami nanodevices allow us to mimic cellular functions in a rationally controlled manner. They describe machineries which respond to environmental stimuli by conducting different tasks. To date, this mostly is achieved by constructing conformational two-state switches which upon activation by stimuli change their conformation resulting in the performance of a priorly programmed task. Their applicability however is often limited to a single, specific stimuli - output combination due to their intrinsic properties as two-state systems only. This makes expanding them further to include multiple stimuli/ outputs challenging. Here, we address this problem by introducing reconfigurable DNA origami arrays as a coupled network of two-state systems. We use this network to create a universal design strategy in which different operational units can be incorporated into any two-state system of our nanorobot. The resulting nanorobot is capable of receiving different stimuli, computing the response to the received stimuli using multi-level Boolean logic gating and yielding multiple programmed output operations with controlled order, timing and spatial position. We expect that this strategy will be a crucial step towards further developing DNA origami nanorobots for applications in various technological fields.

biophysics↗

bioRxiv2023

Super-Resolved FRET and Co-Tracking in pMINFLUX

Single-molecule FRET (smFRET) is widely used to investigate dynamic (bio) molecular interactions taking place over distances of up to 10 nm. With the advent of recent super-resolution methods such as MINFLUX, MINSTED or RASTMIN, the spatiotemporal resolution of these techniques advanced towards the smFRET regime. While these methods do not suffer from the spatial restriction of FRET, they only visualize one emitter at a time, thus rendering fast dynamics of interactions out of reach. Here, we describe two approaches to overcome this limitation in pMINFLUX using its intrinsic fluorescence lifetime information. First, we combined pMINFLUX with smFRET. This enabled us to track a FRET donor fluorophore and simultaneously colocalize its FRET acceptor with nanometer precision. To extend co-localized tracking beyond the FRET range, we developed pMINFLUX lifetime multiplexing, a method to simultaneously track two fluorophores with similar spectral properties but distinct fluorescence lifetimes. We demonstrated its application on both static and dynamic DNA origami systems with a precision better than 2 nm. Within the FRET range, pMINFLUX lifetime multiplexing additionally uses a novel combined phasor-microtimegating approach. This paves the way for nanometer precise co-localized tracking for inter-dye distances between 4 nm and 100 nm, closing the resolution gap between smFRET and co-tracking. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/534096v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@11459forg.highwire.dtl.DTLVardef@1f1cee2org.highwire.dtl.DTLVardef@4592e6org.highwire.dtl.DTLVardef@1af3e48_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis

Crossovers, the exchange of homolog arms, are required for accurate segregation during meiosis. Studies in yeast have established that the single end invasion intermediate is highly regulated to ensure crossover distribution. Single end invasions are thought to differentiate into double Holliday junctions that are resolved by MutLgamma (MLH1/3) into crossovers. Currently, we lack knowledge of early steps of mammalian crossover recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination and cytology, we infer that polymerized single-end invasion intermediates and nicked double Holliday junctions are crossover precursors in mouse spermatocytes. In marked contrast to yeast, MLH3 plays a structural role to differentiate single end invasions into double Holliday junctions with differentially polymerized 3 ends. Therefore, we show independent genetic requirements for precursor formation and asymmetry with regard to 3 end processing, providing mechanistic insight into crossover formation and patterning.

genetics↗