Descrizione del progetto
Sfruttare le connessioni tra cranio e meningi per controllare le patologie cerebrali
Dato che sempre più persone in tutto il mondo vivono più a lungo, la società si confronta con le crescenti sfide derivanti dalle malattie neurodegenerative, che interessano milioni di persone. La recente scoperta delle connessioni tra cranio e meningi in grado di mediare il traffico delle cellule immunitarie diretto al cervello è estremamente promettente per diagnosi e trattamenti nuovi. Tuttavia, le caratteristiche cellulari e strutturali comprensive delle connessioni tra cranio e meningi, nonché cranio/calotta cranica necessitano di ulteriori ricerche. Il progetto CALVARIA, finanziato dall’UE, impiegherà le tecnologie sperimentali avanzate di chiarificazione dei tessuti, proteomica e sequenziamento dell’RNA a cellula singola per indagare i possibili utilizzi della scoperta per un accesso agevolato dal midollo osseo del cranio/della calotta cranica, consentendo una migliore somministrazione dei farmaci nel cervello, il controllo della neuroinfiammazione e un rilevamento più semplice delle patologie cerebrali.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
85764 Neuherberg
Germania