Biology subjects

Sturm, A.

Publications and source records attributed to Sturm, A..

6 recordsLinked to original sources

bioRxiv2024

An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle of Plasmodium falciparum

Current liver-stage Plasmodium falciparum models are complex, expensive, and largely inaccessible, hindering research progress. Here, we show that a 3D liver spheroid model grown from immortalized HepG2/C3A cells supports the complete intrahepatocytic lifecycle of P. falciparum. Our results demonstrate sporozoite infection, development of exoerythrocytic forms, and breakthrough infection into erythrocytes. The 3D-grown spheroid hepatocytes are structurally and functionally polarised, displaying enhanced albumin and urea production and increased expression of key metabolic enzymes, mimicking in vivo conditions - relative to 2D cultures. This accessible, reproducible model lowers barriers to malaria research, promoting advancements in fundamental biology and translational research.

microbiology↗

bioRxiv2024

Nanomotion technology for testing azithromycin susceptibility of Salmonella enterica

Azithromycin is used to treat invasive salmonellosis, despite conflicting effective concentrations in vitro and in vivo. Resistance of Salmonella enterica to azithromycin is increasing. We demonstrate that nanomotion technology can be used for rapid phenotypic testing of Salmonellas susceptibility to azithromycin. Nanomotion changes under various culture conditions correlated with susceptibility measured by MIC determination, CFU counting, and fluorescent reporter-based estimates of intrabacterial azithromycin accumulation.

microbiology↗

bioRxiv2024

Conformational dynamics of electrostatically charged Intrinsically Disordered Proteins

We experimentally and computationally study the dynamics of homogeneously electrically charged intrinsically disordered proteins (IDPs) in ionic solutions (aqueous solutions containing salt). Computationally, this is achieved by extending a recently introduced discrete elastic rod (DER) model to include electrostatic interactions. The respective model includes only three free parameters: bending stiffness, bond length, and hydrodynamic radius. These parameters were obtained by fitting the measured conformational dynamics of uncharged polypeptides as reported in a previous publication [8]. We compare our computational results with photo-electron transfer fluorescence correlation spectroscopy (PET-FCS) measurements of the conformational dynamics of the highly charged (-44 e-) intrinsically disordered protein Prothymosin . We here report on an agreement between the loop-closing rates obtained from our computational model and the respective experimental measurements, with rate values significantly slower than those observed for uncharged IDPs.

biophysics↗

bioRxiv2022

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

genomics↗

bioRxiv2022

Antibiotic action revealed by real-time imaging of the mycobacterial membrane

The current understanding of mycobacterial cell envelope remodeling in response to antibiotics is limited. Chemical tools that report on phenotypic changes with minimal cell wall perturbation are critical to understanding such time-dependent processes. We employed a fluorogenic chemical probe to image how antibiotics perturb mycobacterial cell envelope assembly in real-time. Time-lapse microscopy revealed that differential antibiotic treatment elicited unique cellular phenotypes, providing a platform for simultaneously monitoring cell envelope construction and remodeling responses. Our data show that rifampicin, which does not directly inhibit cell wall biosynthesis, affords a readily detected mycomembrane phenotype. The fluorogenic probe revealed the production of extracellular vesicles in response to antibiotics, and analyses of these vesicles indicate that antibiotic treatment elicits the release of agents that attenuate macrophage activation.

microbiology↗

bioRxiv2017

Genetic fingerprinting of salmon louse (Lepeophtheirus salmonis) populations in the North-East Atlantic using a random forest classification approach

Caligid sea lice represent a significant threat to salmonid aquaculture worldwide. Lepeophtheirus salmonis is the predominant species that occurs in the Northern Hemisphere. Dispersal of sea lice between marine aquaculture sites and geographic regions is thought to occur rapidly via planktonic transport of larvae. Population genetic analyses have consistently shown minimal population genetic structure in North Atlantic L. salmonis, frustrating efforts to track louse populations, improve targeted control measures and understand local adaption to environmental conditions. The aim of this study was to test the power of reduced representation library sequencing (IIb-RAD sequencing) coupled with random forest machine learning algorithms to define markers for fine-scale discrimination of louse populations. We identified 1286 robustly supported SNPs among four L. salmonis populations from Ireland (N=2, 27 individuals), Scotland (N=1, 11 individuals) and North Norway (N=1, 12 individuals). Weak global structure (FSC = 0.018, p<0.0001) and only one significant pairwise FST comparison was observed (Scotland vs Kenmare Bay, (FST = 0.018, p<0.0001)) using all 1286 SNPs. The application of a random forest machine-learning algorithm identified 98 discriminatory SNPs that dramatically improved population assignment (DAPC assignment probability = 1), increased global Fsc = 0.098, (p<0.0001) and resulted in pairwise comparisons that all showed highly significant Fst-values (range = 0.081 - 0.096, p<0.0001). Out of 19 SNPs found to be under directional selection between populations, 12 corresponded to the discriminatory SNPs identified using random forest. Taken together our data suggest that L. salmonis SNP diversity exists with which it is possible to discriminate differences between nearby populations given suitable marker selection approaches, and that such differences might have an adaptive basis. We discuss these data in light of sea lice adaption to anthropogenic and environmental pressures as well as novel approaches to track and predict sea louse dispersal.

ecology↗