Biology subjects

Koester, D.

Publications and source records attributed to Koester, D..

7 recordsLinked to original sources

bioRxiv2025

Active flows drive clustering and sorting of membrane components with differential affinity to dynamic actin cytoskeleton

Several cell membrane proteins, including signalling receptors and cell adhesion receptors, bind to contractile cortical F-actin at the cytoplasmic leaflet. Interaction with contractile actomyosin and associated actin flows drives these proteins into nanoscale clusters and mesoscopic assemblies of physiological relevance. In the context of diverse actin-binding membrane proteins, we ask how a specific composition of the local cluster/assembly may be achieved. Using in vitro reconstitution together with kinetic Monte Carlo simulations our studies reveal that an interplay between differential actin-binding affinity, protein-protein interactions and actomyosin remodelling leads to specific molecular patterning within a cluster and sorting between clusters. We show that in the lamellipodia of spreading cells in vivo, actin flows also result in the sorting of high and low-affinity actin-binders. This affinity-based sorting mechanism provides an attractive means for locally controlling cell membrane composition via engagement with the active cortical meshwork beneath.

cell biology↗

bioRxiv2025

ADAM-tRNA-seq: An Optimized Approach for Demultiplexing and Enhanced Hierarchal Mapping in Direct tRNA Sequencing

Transfer RNAs (tRNAs) play an essential role in protein synthesis and cellular homeostasis, with their dysregulation associated with various human pathologies. Recent advances in direct RNA sequencing by the Nanopore platform have enabled simultaneous profiling of tRNA abundance, modifications, and aminoacylation status. However, the high sequence similarity among tRNAs and the lack of robust demultiplexing strategies reduce the accuracy and limit the scalability of current approaches. Here, we developed ADAM-tRNA-seq, a framework that addresses two key limitations of the Nanopore-based direct tRNA sequencing. First, we develop an RNA-based barcode demultiplexing method, employing a barcode embedded within the sequencing adapter that is recognized by the Dorado basecaller. Second, we designed a hierarchy-based mapping strategy that mitigates read loss due to multimapping by classifying reads at the isodecoder, isoacceptor, or isotype levels, thereby enhancing quantification accuracy. We validated ADAM-tRNA-seq using both synthetic tRNAs and a complex human tRNA pool, and systematically optimized it to achieve up to 99% classification precision. Together, these developments enable more accurate, scalable, and comprehensive characterization of tRNA pools in diverse sample types.

biochemistry↗

bioRxiv2020

Acoustic stimulation increases implicit adaptation in sensorimotor adaptation

Sensorimotor adaptation is an important part of our ability to perform novel motor tasks (i.e., learning of motor skills). Efforts to improve adaptation in healthy and clinical patients using non-invasive brain stimulation methods have been hindered by interindividual and intra-individual variability in brain susceptibility to stimulation. Here, we explore unpredictable loud acoustic stimulation as an alternative method of modulating brain excitability to improve sensorimotor adaptation. In two experiments, participants moved a cursor towards targets, and adapted to a 30{degrees} rotation of cursor feedback, either with or without unpredictable acoustic stimulation. Acoustic stimulation improved initial adaptation to sensory prediction errors in Study 1, and improved overnight retention of adaptation in Study 2. Unpredictable loud acoustic stimulation might thus be a potent method of modulating sensorimotor adaptation in healthy adults.

neuroscience↗

bioRxiv2020

Geological degassing enhances microbial metabolism in the continental subsurface

Mantle degassing provides a substantial amount of reduced and oxidized gases shaping microbial metabolism at volcanic sites across the globe, yet little is known about its impact on microbial life under non-thermal conditions. Here, we characterized deep subsurface fluids from a cold-water geyser driven by mantle degassing using genome-resolved metagenomics to investigate how the gases impact the metabolism and activity of indigenous microbes compared to non-impacted sites. While species-specific analyses of Altiarchaeota suggest site-specific adaptations and a particular biogeographic pattern, chemolithoautotrophic core features of the communities appeared to be conserved across 17 groundwater ecosystems between 5 and 3200 m depth. We identified a significant negative correlation between ecosystem depth and bacterial replication, except for samples impacted by high amounts of subsurface gases, which exhibited near-surface activity. Our results suggest that geological degassing leads to higher nutrient flows and microbial activity in the deep subsurface than previously estimated.

microbiology↗

bioRxiv2019

Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age

BackgroundCortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups. ObjectiveWe examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort. MethodsIn a within-subject design, subjects (n = 17, 55.7 {+/-} 1.0 years, 9 female) received auditory click stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to those reported previously in a younger cohort (n = 11, 24.2 {+/-} 0.9 years, 8 female). ResultsOvernight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups. ConclusionsOur findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations. HighlightsO_LIAuditory closed-loop stimulation induced SOs and sleep spindles in older subjects C_LIO_LIStimulation effects were reduced and overall susceptibility diminished with age C_LIO_LISlow oscillation and sleep spindle dynamics deviated from those in younger subjects C_LIO_LIStimulation shows no evidence for memory effect in older subjects C_LI

neuroscience↗

bioRxiv2018

Lack of functional caveolae in Cav3 mutated human dystrophic myotubes results in deficient mechanoprotection and IL6/STAT3 mechanosignaling.

Caveolin-3 is the major structural protein of caveolae in muscle cells. Mutations in the CAV3 gene cause different type of muscle disorders mostly characterized by defects in membrane integrity and repair, deregulation in the expression of various muscle proteins and deregulation of several muscle associated signaling pathways. We show here that myotubes derived from patients bearing the CAV3 P28L and R26Q mutations present a lack of functional caveolae at the plasma membrane which results in an abnormal mechanoresponse. Mutant myotubes can no longer buffer the increase of membrane tension induced by mechanical stress and present an hyperactivation of the IL6/STAT3 signaling pathway at rest and under mechanical stress. The impaired mechanical regulation of the IL6/STAT3 signaling pathway by caveolae leads to chronic activation and a higher expression of muscle specific genes. These defects could be reversed by reassembling a pool of functional caveolae through expression of wild type Cav3. Our findings bring more mechanistic insight into human Cav3 associated muscle disorders and show a general defect in the mechanoresponse of CAV3 P28L and R26Q myotubes.

cell biology↗

bioRxiv2017

Revealing intricate acto-myosin dynamics at a membrane surface using interferometric scattering microscopy

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect, and image individual membrane attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as a function of ATP concentration, providing evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network. Statement of SignificanceHere, we show that interferometric scattering microscopy in combination with single particle tracking enables label-free, high contrast imaging of filament dynamics on surfaces, while distinguishing different species based on their mass. These results significantly broaden the available toolkit, and associated capabilities of researchers studying dynamics of biological machines at interfaces.

biophysics↗