Biology subjects

Balkenhol, J.

Publications and source records attributed to Balkenhol, J..

6 recordsLinked to original sources

bioRxiv2026

A trajectory-coupled network bottleneck governs gemcitabine resistance in 3D PDAC tissue models

PDAC exhibits rapid chemoresistance, yet how drug-tolerant states arise remains unclear. Existing approaches miss how network topology evolves across cell-state transitions under drug pressure. A 3D PANC-1 tissue model on decellularized intestinal matrix was used for scRNA-seq across four conditions (control, GEM, TGF-{beta}1, GEM+TGF-{beta}1). Pseudotime trajectory inference was combined with dynamic PPI network analysis. Findings were cross-examined in a PDAC atlas (726,107 cells, 231 patients; Loveless et al., 2025). GEM resistance involved E2F1, mTOR, CDK1, AURKA, TPX2, TOP2A, and BIRC5. TGF-{beta}1 drove EMT resistance via KRAS, glycolysis, and hypoxia, inducing SPOCK1, MBOAT2, COL5A1, ADAMTS6, THBS1, and FN1. Trajectory-coupled network analysis revealed an emergent bottleneck when G1[->]S and TGF-{beta}1-induced EMT co-occurred: CDK1 centrality spiked selectively, with CDKN1A as critical regulator. This CDK1-CDKN1A-WEE1 axis defines an "S-phase persistence" state enriched for GEM survivors. Atlas cross-examination confirmed 8.7-fold metastatic enrichment of triple-positive cells and EMT-cell-cycle coupling. Trajectory-coupled network topology analysis identifies CDK1-CDKN1A-WEE1 as a chemoresistance bottleneck corroborated in 726,107 patient cells. The framework generalizes to drug resistance across cancer types.

systems biology↗

bioRxiv2024

Thrombo-inflammation analyzed in a validated seven-layer platelet decision model: cellular decisions are tough problems fast and heuristically solved

Decisions in biology happen fast and are driven by evolution to optimize survival chances. In platelets, this is achieved by organizing signaling cascades into rapid decision-funnels with modulatory crosstalk. We show that network decision processes underlying cellular decisions are tough to solve (equivalent to classical satisfiability problems, SAT). Hence, heuristics, modular decision-making, and decision funnels are required for efficient decisions. We establish this using a seven-layer platelet decision network that agrees well with all available genetic and functional experimental data. Platelet decision cascades are robust to perturbations: For example, receptors such as TRPM7 modulate platelet activity. However, knockouts of the receptors still leave platelets reactive overall. Dynamic control resolves relaying functions from kinases to cytoskeleton alterations. This allows fast execution of platelet shape change or aggregation. Stress conditions can shift platelet decision funnels towards constant activation of aggregation or immune signaling, causing thrombosis or thrombo-inflammation. Based on the network dynamics, we conclude that platelets pragmatically resolve the complex (non-polynomial (NP)) cellular decision problems by using a similar relaxation to those proposed in mathematics - many different configurations end up in similar states. Metamathematical considerations (no mathematical proof) suggest that NP problems are more complex then P problems. One sentence abstractWe show that cellular decision problems like the platelet signaling cascade may need unexpectedly long to solve but in general, they are efficiently solved using heuristics ("decision funnels"), implying fast decisions but the risk of chronic stress and inflammation.

bioinformatics↗

bioRxiv2022

Modelling non-local neural information processing in the brain

The representation of the surrounding world emerges through integration of sensory information and actions. We present a novel neural model which implements non-local, parallel information processing on a neocolumnar architecture with lateral interconnections. Information is integrated into a holographic wave interference pattern. We compare the simulated in silico pattern with observed in vivo invasive and non-invasive electrophysiological data in human and non-human primates. Our model replicates the modulation of neural high-frequency activity during visual perception showing that phase-locked low and high-frequency oscillations self-organize efficiently and carry high information content. The simulation further models how criticality (high content) of information processing emerges given a sufficiently high number of correlated neurons. Non-local information processing, forming one holographic wave pattern, suggests a platform for emergence of conscious perception. One sentence summarySimulated non-local information processing on a neocolumnar architecture models well multiple electrophysiological observations of brain activity, including high-frequency activity during visual perception in primates.

neuroscience↗

bioRxiv2021

Dual-color Fluorescence Cross-Correlation Spectroscopy to study Protein-Protein Interaction and Protein Dynamics in Live Cells

We present a protocol and workflow to perform live cell dual-color fluorescence crosscorrelation spectroscopy (FCCS) combined with Forster Resonance Energy transfer (FRET) to study membrane receptor dynamics in live cells using modern fluorescence labeling techniques. In dual-color FCCS, where the fluctuations in fluorescence intensity represents the dynamical "fingerprint" of the respective fluorescent biomolecule, we can probe co-diffusion or binding of the receptors. FRET, with its high sensitivity to molecular distances, serves as a well-known "nanoruler" to monitor intramolecular changes. Taken together, conformational changes and key parameters such as local receptor concentrations, and mobility constants become accessible in cellular settings. Quantitative fluorescence approaches are challenging in cells due to high noise levels and the vulnerable sample itself. We will show how to perform the experiments including the calibration steps. We use dual-color labeled {beta}2-adrenergic receptor ({beta}2AR) labeled (eGFP and SNAPtag-TAMRA). We will guide you step-by-step through the data analysis procedure using open-source software and provide templates that are easy to customize. Our guideline enables researchers to unravel molecular interactions of biomolecules in live cells in situ with high reliability despite the limited signal-to-noise levels in live cell experiments. The operational window of FRET and particularly FCCS at low concentrations allows quantitative analysis near-physiological conditions. Link to accompanying video: https://tr240.uni-wuerzburg.de/vippclass/index.php/s/TL8aWmwE9RjGfLE

biophysics↗

bioRxiv2021

How biological cells including platelets and megakaryocytes decide complex problems fast but risky

Short AbstractMathematical decision processes are accurate but sometimes take very long time or simply do not happen. Decisions in biology happen fast and driven by evolution, optimizing survival chances. This results in stochastic decisions with on average good adaptation to the environment but an inherent risk of individual errors e.g. developing cancer during cell regeneration. We calculate and show in platelets and megakaryocytes how cellular decision processes increases risk for errors and inflammation. Short cut solutions adapted from nature improve computer strategies for protein folding and network decision processes. Complex problems are not always solved in foreseeable time, instead the fast solutions in biology speed up errors everywhere including biochemical aging of blood vessels, misfolded proteins, mis-programmed cells, cancer and heart failure. One sentence abstractWe investigate in biological networks how complex decision problems are mastered not by an accurate but unforeseeable long mathematical search but rather pragmatic and fast, with an inherent risk of error, a basis for inflammation and cancer.

bioinformatics↗

bioRxiv2019

Quantifying and modelling non-local information processing of associative brain regions

Short abstractBrain world representation emerges not by philosophy but from integrating simple followed by more complex actions (due to drives, instincts) with sensory feedback and inputs such as rewards. Our simulation provides this world representation holistically by identical information encoded as holographic wave patterns for all associative cortex regions. Observed circular activation in cell culture experiments provides building blocks from which such an integrative circuit can evolve just by excitation and inhibition transfer to neighbouring neurons. Large-scale grid-computing of the simulation brought no new emergent phenomena but rather linear gains and losses regarding performance. The circuit integrates perceptions and actions. The resulting simulation compares well with data from electrophysiology, visual perception tasks, and oscillations in cortical areas. Non-local, wave-like information processing in the cortex agrees well with EEG observations such as cortical alpha, beta, and gamma oscillations. Non-local information processing has powerful emergent properties, including key features of conscious information processing.

neuroscience↗