Descrizione del progetto
Un nuovo studio indaga le interazioni che alterano la produzione di mielina
L’alterazione della produzione di mielina nel nostro corpo comporta gravi malattie quali la sclerosi multipla. Il progetto OLI.VAS finanziato dall’UE, indagherà le interazioni molecolari tra i vasi sanguigni e gli oligodendrociti, cellule gliali che producono mielina nel sistema nervoso centrale. Ricerche recenti indicano che i vasi sanguigni non solo forniscono ossigeno e sostanze nutritive ma regolano anche attivamente lo sviluppo e la funzione degli organi. In questo senso, i ricercatori coinvolti nel progetto OLI.VAS hanno scoperto che i segnali provenienti dai vasi controllano direttamente la produzione di cellule precursori degli oligodendrociti in una cosiddetta interfaccia oligo-vascolare. Applicando un approccio multidisciplinare, i ricercatori intendono individuare le interazioni molecolari tra vasi sanguigni e oligodendrociti durante lo sviluppo e l’omeostasi, come pure nelle condizioni di malattie demielinizzanti.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
53127 Bonn
Germania