Lipid transport across the blood-brain barrier

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In this project we aim to elucidate the selective lipid transport across the blood brain barrier (BBB) and the role of the major fascilitator superfamily domain-containing protein 2a (Mfsd2a) for this process. We want to test the hypothesis that, while initially involving Mfsd2a, the acting barrier that mediates selective lipid import into the brain in fact is a multi-stage process and includes local lipid metabolism. The project will study the individual contribution of the participating major cell types of the BBB, capillary endothelial cells and astrocytes, by characterizing their activities in lipid uptake, metabolism and trafficking. Also the role of cell-cell-connectivity for these processes will be investigated. Using the mouse model, complementary research at increasing complexity levels (in vitro and in vivo) will be conducted. The project will employ the novel alkyne lipid tracer technology that has opened a new era in lipid biology and metabolism research. These non-radioactive tracers are fully compatible with the suit of modern analytical methods and therefore allow for correlative tracking of lipid localization and metabolism at the highest spatial and analytical resolution in an unprecedented manner. We will combine alkyne lipid tracing with state-of-the-art analytics, including super-resolution microscopy and quantitative mass spectrometry (MS) lipidomics. Benefitting from this technological edge this proposal will yield important insights into the complex process of selective lipid uptake into the mammalian brain.