Biology subjects

Kotter, M. R.

Publications and source records attributed to Kotter, M. R..

2 recordsLinked to original sources

bioRxiv2026

imAgeScore, a Cell Painting-Based Predictor of Cellular Age for High-throughput Drug Screening Applications

Quantifying cellular age in vitro in a scalable and biologically meaningful manner is essential for the discovery of pharmacological interventions that modulate aging. We developed imAgeScore, a machine-learning model trained on high-content Cell Painting features to predict the phenotypic age of primary human dermal fibroblasts. imAgeScore correlates with chronological and DNA methylation-based age estimates and captures coordinated morphological changes across nuclear and cytoplasmic compartments. The model detected age acceleration during serial propagation and age reduction following partial reprogramming. Pharmacological interventions targeting distinct aging hallmarks induced predictable shifts in predicted age and enabled classification of damaging versus rejuvenating cellular states. Application of imAgeScore in an automated high-throughput screening pipeline identified candidate age-modulating compounds, revealed inter-individual variability in response magnitude, and detected additive rejuvenation effects in selected combinatorial treatments. Functional validation in a scratch wound assay confirmed enhanced cellular repair by leading candidates, supporting the biological relevance of morphology-derived age reduction. Together, these results demonstrate that image-based morphological profiling provides a scalable platform for quantifying cellular aging and screening for candidate rejuvenation interventions.

cell biology↗

bioRxiv2018

Energetic substrate availability regulates synchronous activity in an excitatory neural network

Neural networks are required to meet significant metabolic demands associated with performing sophisticated computational tasks in the brain. The necessity for efficient transmission of information imposes stringent constraints on the metabolic pathways that can be used for energy generation at the synapse, and thus low availability of energetic substrates can reduce the efficacy of synaptic function. Here we study the effects of energetic substrate availability on global neural network behavior and find that glucose alone can sustain excitatory neurotransmission required to generate high-frequency synchronous bursting that emerges in culture. In contrast, obligatory oxidative energetic substrates such as lactate and pyruvate are unable to substitute for glucose, indicating that processes involving glucose metabolism form the primary energy-generating pathways supporting coordinated network activity. Our experimental results are discussed in the context of the role that metabolism plays in supporting the performance of individual synapses, including the relative contributions from postsynaptic responses, astrocytes, and presynaptic vesicle cycling. We propose a simple computational model for our excitatory cultures that accurately captures the inability of metabolically compromised synapses to sustain synchronous bursting when extracellular glucose is depleted.

neuroscience↗