Biology subjects

Brettschneider, J.

Publications and source records attributed to Brettschneider, J..

4 recordsLinked to original sources

bioRxiv2026

Embedded transport accelerates interaction-limited biosensing

Phenotypic biosensors that measure bacterial viability and antimicrobial susceptibility are essential for rapid infectious disease diagnostics, yet their speed is fundamentally limited by the rate at which bacteria encounter reporter molecules, a transport bottleneck that has been typically addressed by complex microfluidic solutions. Here we show that this bottleneck can be overcome by engineering transport directly into the sensing material. A multifunctional ionic hydrogel matrix, co-encapsulating bacterial growth medium and the redox reporter resazurin, exploits swelling-driven convective transport to dramatically accelerate bacteria-reporter interactions without any change to assay chemistry. By systematically tailoring the hydrogel crosslinking density and optimizing the encapsulated nutrient-osmotic microenvironment, we maximize metabolic signal generation to achieve a 12-to-48-fold reduction in detection time relative to solution-phase and conventional hydrogel assays. Deployed in a standard 96-well format for urinary tract infection (UTI) diagnosis of 48 clinical samples, the platform rapidly detects infection in 15 minutes to 2 hours, achieving 95% sensitivity and 100% specificity for bacterial detection, and 100% sensitivity and 98% specificity for antimicrobial susceptibility profiling, compared to time-consuming gold-standard urine culture-based methods. Results are readable both quantitatively on a plate reader and visually as a colorimetric assay, enabling point-of-care deployment without additional instrumentation. Thus, embedding transport enhancement within the sensing matrix, represents a general and scalable design principle for accelerating interaction-limited biosensing, which has excellent scope for rapid diagnostic development.

bioengineering↗

bioRxiv2025

Dynamic Bacterial Growth Modulation in Structurally Distinct and Functionally Tuneable Agarose Hydrogels

Bacterial adaptability to diverse environments drives infection, persistence, and antibiotic resistance. Although hydrogels are increasingly used to model such conditions, the factors governing hydrogel-dependent bacterial growth is complex. Here, we focus on agarose hydrogels and investigate how their material properties influence bacterial proliferation. Using two agarose types - hydroxyethyl substituted and unsubstituted - at varying concentrations, we tested four bacterial species (E. coli, P. fluorescens, S. aureus, B. subtilis) across five nutrient media yielding 120 conditions. Growth consistently decreased with increasing hydrogel stiffness and water loss in unsubstituted and substituted agarose hydrogels, regardless of species. Media effects were largely due to their impact on hydrogel properties rather than nutrient content. Furthermore, electrostatic repulsion between Gram positive bacteria and anionic unsubstituted agarose suppressed growth in high concentration gels. These findings demonstrate that bacterial growth in agarose systems is primarily shaped by gel mechanics and surface interactions, informing the design of infection models and antibacterial materials.

microbiology↗

bioRxiv2025

RNA modifications on Adenosine co-Regulate Macrophage Function

Macrophages are a highly plastic innate immune cell subset that depends on environmental cues to activate, execute and resolve inflammatory responses. This plasticity of function is mirrored by the diversity of RNA modifications that dynamically decorate macrophage transcripts. Here, using the mouse macrophage line RAW 264.7 (RAW), we addressed the combinatorial effect of two major mRNA modifications: adenosine to inosine (A-to-I) deamination by ADAR1 and adenosine N6-methylation (m6A) by METTL3. Using both short-read and single molecule sequencing on RAW macrophages with genetic deletions of ADAR1 or METTL3, we identified transcripts that were modified by both enzymes, with specific functional outcomes on macrophage activation. While m6A levels remained relatively stable even in the absence of ADAR1, loss of METTL3 led to a global reduction in A-to-I editing levels. This interrelation was most apparent when m6A sites were distant from sites of deamination, suggesting a possible function of m6A in ADAR1-mediated editing. Using a dual reporter cell line where guided ADAR1 recruitment can be measured via eGFP reactivation, we observed that m6A modification of ADAR-engager guide RNAs substantially improved targeted RNA editing. Overall, we report the first example of an interdependence between modifications, which can also be therapeutically exploited.

immunology↗

bioRxiv2019

Quantifying uncertainty in brain-predicted age using scalar-on-image quantile regression

Prediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysis. We propose a penalised functional quantile regression model of age on brain structure with cognitively normal (CN) subjects in the Alzheimers Disease Neuroimaging Initiative (ADNI), and use it to predict brain age in Mild Cognitive Impairment (MCI) and Alzheimers Disease (AD) subjects. Unlike the machine learning approaches available in the literature of brain age prediction, which provide only point predictions, the outcome of our model is a prediction interval for each subject.

neuroscience↗