Project description
New study investigates the interactions that disrupt myelin production
The disruption of myelin production in our body leads to serious diseases such as multiple sclerosis. The EU-funded OLI.VAS project will study the molecular interactions between blood vessels and oligodendrocytes – glial cells that produce myelin in the central nervous system. Recent research indicates that not only do blood vessels supply oxygen and nutrients, but they also actively regulate organ development and function. In this regard, the researchers involved in OLI.VAS have discovered that the signals coming from vessels directly control the generation of oligodendrocyte precursor cells at a so-called oligo-vascular interface. By applying a multidisciplinary approach, researchers plan to identify molecular interactions between blood vessels and oligodendrocytes during development and homeostasis as well as in conditions of demyelinating diseases.
Objective
Oligodendrocytes (OLs) are the glia cells that produce myelin in the central nervous system (CNS). Despite the severe outcome of demyelinating diseases, like multiple sclerosis (MS), little is known about the mechanisms by which myelin is disrupted or why remyelination fails in disease. Thus, a substantial advance in the understanding of oligodendrocyte biology and myelin pathology is required in order to develop successful treatments for demyelinating diseases.
Recent research indicates that apart from delivering oxygen and nutrients, blood vessels are active regulators of organ function. Our recent work supports the existence of an oligo-vascular interface where vessels directly control oligodendrogenesis. However, mechanistic insights of the interaction between OLs and the vasculature are lacking. Based on the innovative hypothesis that proper generation and OL functionality depends on active crosstalk with the vasculature, the OLI.VAS project will now tackle the challenge to characterize in depth the interaction between OLs and the vasculature during development and demyelinating diseases.
To achieve this goal, two complementary multidisciplinary research tracks are pursued:
Research track 1: Deconstructing and reconstructing the oligo-vascular interface to unravel the relationship of oligodendrocyte lineage cells with the vasculature
Research track 2: Studying the oligo-vascular interface in white matter lesions. Modulating the vasculature to prevent de-myelination or promote of re-myelination
Both tracks combine cutting edge technology in single cell and spatial transcriptomics, bioinformatics, 3D imaging, in vitro and ex vivo tissue culture, mouse genetics and MS patient samples.
OLI.VAS will deliver new insights into the role of the vasculature as a regulator of oligodendrogenesis and myelination and thus generate major scientific breakthroughs in an area that is highly relevant for diseases such as MS, which affects more than 600000 patients in Europe.
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Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
53127 Bonn
Germany