FUNCTIONAL ARCHITECTURE OF CNS-ENDOTHELIAL INTERFACES

• Applicant: Professorin Dr. Amparo Acker-Palmer
• Subject Area: Developmental Neurobiology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564162002

Blood vessels, long known for their role in delivering oxygen and nutrients, are increasingly recognized as key signaling systems that regulate the development and homeostasis of the central nervous system (CNS). The endothelium plays a pivotal role by forming critical interfaces with surrounding cells, enabling molecular crosstalk essential for maintaining proper organ structure and function. Disruptions in these interactions are implicated in a wide range of neurodevelopmental and neurodegenerative diseases. While we are gaining a better understanding of how neuronal and vascular systems work together during development, much remains unknown about how proteins are arranged and interact at functional cellular interfaces within their natural tissue environment. This gap in knowledge is largely due to technological limitations. The amount and interaction of proteins at these specific subcellular locations are key to understanding the physiological properties of these cellular regions, which in turn shape the larger organization and function of interconnected cellular networks. Building on our previous groundbreaking discoveries in the neurovascular field, the goal of this project is to explore the molecular dynamics and quantitative aspects of cellular communication at endothelial interfaces in the brain, with a focus on uncovering entirely new interfaces that can only be observed at subcellular resolutions. To achieve this, we will employ cutting-edge imaging technologies, including expansion microscopy and high-resolution 3D tissue microscopy, alongside functional analyses using in vivo mouse genetics. This approach will allow us to push the boundaries of our current understanding and uncover previously uncharted aspects of neurovascular biology.

• DFG Programme: Reinhart Koselleck Projects