Projektbeschreibung
Die Verbindungen zwischen Schädel und Hirnhaut zur Behandlung von Hirnerkrankungen nutzen
Da Menschen weltweit immer länger leben, steht die Gesellschaft vor wachsenden Problemen mit Millionen Fällen von neurodegenerativen Erkrankungen. Erst vor Kurzem wurden die Schädel-Hirnhaut-Verbindungen entdeckt, die den Immunzelltransport in das Gehirn vermitteln können. Sie scheinen für eine neue Diagnostik und neuartige Behandlungen vielversprechend zu sein. Doch die umfassenden zellulären und strukturellen Eigenschaften der Schädel-Hirnhaut-Verbindungen sowie von Schädel und Schädeldecke müssen noch tiefer erforscht werden. Im EU-finanzierten Projekt CALVARIA kommen hoch komplexe experimentelle Technologien der Gewebeklärung, Proteomik und Einzelzell-RNA-Sequenzierung zum Einsatz, um herauszuarbeiten, ob sich diese Entdeckung für diverse Zwecke nutzen lassen könnte: nämlich, um einen leichteren Zugang zum Knochenmark von Schädel und Schädeldecke zu erlangen, um den Wirkstofftransport ins Gehirn zu verbessern, um Neuroinflammationen einzudämmen oder um Hirnpathologien einfacher zu erkennen.
Ziel
Neurodegenerative diseases (NDs) are labeled as the epidemic of the 21st century. The inflammation of the brain is a common pathology observed in many NDs. Here I aim to exploit our discovery of skull – meninges connections (SMCs) mediating immune cell trafficking into the brain to ease this healthcare burden. Using tissue clearing methods, we found that the skull (calvaria) bone marrow is directly connected to the brain meninges, a discovery that was also shown by an independent group around the same time. This finding suggests that the calvaria is involved in diverse brain pathologies. Easier accessibility of the calvaria compared to brain parenchyma also makes it an attractive region to target, which would alleviate hurdles of drug delivery into the brain, e.g. to control neuroinflammation. Furthermore, potential biomarkers in the calvaria reflecting pathologies of the brain could be easier and faster to detect. However, the detailed structural and cellular characteristics of the SMCs and the calvaria, and how they correlate and interact with neuropathology remain unknown. Here, we will utilize high-throughput technologies such as tissue clearing, single cell RNAseq, proteomics and unbiased analysis of data using deep learning to close this knowledge gap. We will use ischemic stroke and dementia models that are associated with acute and chronic neuroinflammation, respectively, and study both mouse and human tissues in parallel to validate potential clinical implications.
This project will investigate followings:
Aim 1 | Calvaria in physiological state
Aim 2 | Therapeutic aspect: manipulation of calvaria to control stroke and dementia
Aim 3 | Diagnostic aspect: calvaria imaging to monitor stroke and dementia
Thus, the first in-depth investigation of the calvaria bone in health and disease could deliver novel diagnostic and therapeutic targets to mitigate the increasing burden of neurological diseases.
Wissenschaftliches Gebiet
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicineneurologydementia
- medical and health sciencesbasic medicinepathology
- natural sciencescomputer and information sciencesartificial intelligencemachine learningdeep learning
- medical and health sciencesbasic medicineneurologystroke
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
85764 Neuherberg
Deutschland