Descripción del proyecto
Aprovechar las conexiones cráneo-meninges para controlar las encefalopatías
A medida que más personas de todo el mundo viven más tiempo, la sociedad se enfrenta a desafíos crecientes que surgen de enfermedades neurodegenerativas que afectan a millones de personas. El reciente descubrimiento de las conexiones cráneo-meninges, que pueden mediar en el tráfico de las células inmunitarias al encéfalo, es extremadamente prometedor respecto a nuevos diagnósticos y tratamientos. Sin embargo, es necesario estudiar más las exhaustivas características estructurales y celulares de estas conexiones y del cráneo/la bóveda craneal. El proyecto CALVARIA, financiado con fondos europeos, utilizará tecnologías experimentales avanzadas de limpieza de tejidos, proteómica y secuenciación de ARN de célula única para investigar el posible aprovechamiento del descubrimiento para un acceso más fácil a la médula ósea del cráneo/la bóveda craneal, que permitiría una mejor administración de fármacos en el encéfalo, controlar mejor la neuroinflamación y una detección más sencilla de las encefalopatías.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
85764 Neuherberg
Alemania