Overarching theme: Our lab addresses fundamental questions in biomedical research concerning cellular morphogenesis—a process that controls the shape, size, number, and spatial distribution of biological cells as they collectively organize into multicellular communities. This process is subject to perturbations triggered by various stress signals, including mechanical injury, toxins (e.g., pharmaceutical drugs), and microbial infections. Cells sense these perturbations and adaptively alter their morphology, growth rate, and metabolic fluxes to maintain fitness under stress. 

 

However, the “molecular grammar” rules governing the ability of individual cells to detect stress signals and convert them into actionable forces—reshaping cells and limiting their growth under stress—remain only partially understood. This is a universal, scale-bridging problem that nearly all biological cells must solve. Deciphering how they achieve this task is the core objective of our research.

 

To this end, we utilize an interdisciplinary approach encompassing molecular multi-omics and data analyses of cells before and after perturbation to derive molecular-scale patterns that can predict a set of heuristic rules. These rules can then be plugged into a model to simulate a virtual whole cell-scale morphonetotype and experimentally validated through quantitative cell microscopy and physicochemical analyses.

 

Our ambition is to contribute this knowledge to the creation of what was outlined as the next challenge in Chemistry and Biology after the breakthrough of AlphaFold—the development of a whole-cell model from first principles. It is our hope that this work can also inform new target mechanisms behind adaptations to perturbations in pathogenic cells living on or in the human body. This is especially important in the context of ever-increasing drug resistance, one of the main threats to global health.

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