Advanced Light Microscopy unit – ALM
Karolinska Institutet and KTH Royal Institute of Technology
Research interests
Our research group investigates the fundamental physical principles governing biological processes at the cellular level. We integrate advanced light microscopy with cell and molecular biology to understand the cell’s complex energy landscape and how protein interactions contribute to integrated physiological functions and organismal diversity.
A central focus of our work is the Na,K-ATPase, the vital ion pump responsible for intracellular homeostasis. While traditionally viewed as a “salt pump”, we have pioneered the understanding of its role as a signal transducer:
- Signaling & Apoptosis: We described how the ligand ouabain triggers an oscillating calcium signal that activates the anti-apoptotic factor Bcl-xL. This pathway plays a critical role in protecting cells against apoptosis in conditions like fetal malnourishment, chronic kidney disease, and infections.
- Neuronal Isoforms & Disease: We study mutations in the neuronal isoform of Na,K-ATPase linked to monogenetic diseases such as therapy-resistant epilepsy, dystonia, and cognitive deficits.
- Sub-cellular Dynamics: Using STED and PALM microscopy, we identified the specific localization of the pump in neurons and developed real-time sodium imaging to track recovery after high neuronal activity.
To truly understand the molecular architecture of the cell, we are pushing the boundaries of imaging beyond traditional super-resolution limits:
- nanometer Precision: While STED and PALM reach resolutions of 20–50 nm, the Na,K-ATPase itself has dimensions of less than 10 nm. We utilize MINFLUX nanoscopy to achieve ~2-3 nm precision, effectively bridging the gap between structural biology and cell biology.
- Molecular Organization: MINFLUX allows us to resolve individual pumps within a cluster and track their dynamics in living cells. This enables us to determine whether the pump forms functional domains or entropic spacers, providing a high-resolution map of the glycosylation-dependent distribution of the enzyme.
Group members
- Hjalmar Brismar, Professor
- David Unnersjö-Jess, postdoc
- Devinda Wijewardena, postdoc
- Linnea Påvenius, PhD student
- Bruno Stojcic, PhD student
- Robin Ebbestad, PhD student
- Joan Patrick, Lab manager