Project description
Nutrition and brain repair
The white matter (WM) is the largest part of the brain, encompassing nerve fibres that functionally connect axons from different regions. WM’s volume decreases with ageing and its degeneration is a hallmark of many neurological conditions. Funded by the Marie Skłodowska-Curie Actions programme, the LipidGlia project is interested in the role of metabolism and diet in microglia function and their ability to regenerate the WM after injury. Researchers will investigate perturbations in key mechanisms involved in microglia function during obesity. Results will help elucidate the mechanisms of WM repair and lay the groundwork for future treatments or interventions.
Objective
European population is rapidly aging. While it was commonly believed that brain aging leads to neuronal loss, recent studies found that instead the volume of white matter (WM) decreases and WM lesions develop with age. WM degeneration is also a hallmark of multiple neurological disorders including Alzheimer’s disease or multiple sclerosis. Understanding cellular responses to WM injury is therefore critical for design of regenerative therapies of central nervous system (CNS). The European population is also increasingly overweight. Obesity is associated with higher risk of multiple sclerosis and other neurological diseases and leads to systemic low-grade inflammation modulating functions of the immune cells. While this paradigm has been extensively studied in peripheral tissues, effect of diet on microglial states in CNS is poorly understood. I hypothesise that high-fat diet disrupts metabolic response of microglia to WM injury and impairs regeneration. My proposal aims to identify diet-altered microglial pathways and how to target them for promoting recovery after injury. For this goal, I will use the single cell and spatial transcriptomics to characterize in detail how WM injury and obesity alters cellular phenotypes. However, currently no method can link the metabolic state of the cell with its transcriptome. I will establish method that combines metabolic measurements with single cell RNA-Seq in mouse models of high-fat diet and demyelination. In addition, I propose to integrate spatial transcriptomics with electron microscopy as an innovative approach to visualize lipid-loaded microglia and link their morphology to the transcriptomic state. This project will provide critical new knowledge of mechanisms of WM repair. The fellowship will allow me to become expert in applying and developing genomic technologies to devastating neurological disorders, and deepen leadership and management skills to achieve my career goal of becoming independent investigator.
Fields of science
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesphysical sciencesopticsmicroscopyelectron microscopy
- medical and health sciencesbasic medicineneurologymultiple sclerosis
- medical and health sciencesbasic medicineimmunology
- medical and health scienceshealth sciencesnutritionobesity
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
53127 Bonn
Germany