Cell Biology of Organelle Networks

Objectives and Challenges

Kristine Schauer’s team, “Cellular Biology of Organelle Networks,” studies the architecture of intracellular organelles under controlled cell culture conditions, in both non-pathological and cancerous contexts, by combining bioengineering approaches with advanced 3D imaging techniques. Intracellular organelles constitute higher levels of cellular organization that act as functional intermediaries between the genotype and the phenotype, thereby governing cellular behavior through multiscale integration.

Research Areas / Major Projects

Our team studies how cellular organization arises from the interaction between genetic programs and physical constraints, and how this organization determines cellular functions and responses. In particular, we investigate the interactions between the physical properties of materials, membrane tension, the actin cytoskeleton, and the mechanosensing of organelles, while exploring organelle organization as a biomarker. This fundamental knowledge is also applied to clinical challenges, including the optimization of antibody-drug conjugate (ADC) trafficking and the regulation of PD-L1 trafficking in the context of immune checkpoint inhibitor therapies.

Our team studies the intracellular architecture of organelles in various cellular models. We combine bioengineering approaches—such as microstructuring, 3D photopolymerization of hydrogels, optogenetics, and in vitro reconstitution assays—with quantitative imaging techniques, particularly holotomography. These approaches allow us to analyze which organelles change—and how—during cancer progression, drug treatments, and the development of treatment resistance.

Key Findings, Prospects, and Impacts

Our recent results indicate that tumor aggressiveness converges at the organelle level, particularly in acid endosomes, which serve as a logistical platform for cellular sorting, recycling, and degradation. We have observed that the localization of acid endosomes becomes more peripheral in several models of aggressive cancers, including melanoma and bladder cancer, promoting cellular behaviors such as increased migration and invasion. We are currently investigating the role of membrane properties in endosome localization and evaluating whether organelle signatures can be used as predictive biomarkers for responses to drug treatments.