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Immunometabolic regulation of microglia function in stroke recovery

Project description

Changing microglia phenotypes over the course of stroke

Microglia in the brain oversee brain homeostasis via immunosurveillance, like guards constantly on the lookout for foreign pathogens or invaders. They are also important in brain development, maintenance of neural networks and repair after brain injury including that caused by stroke. Recent evidence suggests that dysfunctional microglia are involved in perpetuating inflammation after stroke. With the support of the Marie Skłodowska-Curie Actions programme, the ImmunoMet project intends to study the dynamic changes in microglial immunophenotype and metabolic pathways over the course of stroke and their potential roles in stroke recovery. The team will use advanced methods including imaging, flow cytometry, metabolomics and single-cell RNA sequencing.

Objective

Stroke is one of the leading causes of death and disability worldwide. Despite recent improvements in stroke prevention and acute treatment, there is still a very urgent need for promoting stroke recovery to improve patients’ quality of life. Microglia are the predominant brain resident immune cells, in charge of brain homeostasis through immune surveillance. Emerging evidences suggest that post-stroke microglial reactivity remains incompletely resolved and persists chronically. ImmunoMet aims to study the impact of persistent inflammatory and dysfunctional traits of microglia during stroke recovery through metabolic reprograming, a set of essential processes key to satisfy the high energetic requirements of immune activation. To fulfill this goal, ImmunoMet will use novel and cutting-edge methodologies, including sophisticated imaging techniques, multiparametric flow cytometry, metabolomics and single-cell RNA sequencing, to investigate the time course evolution of microglia immunophenotype and the potential shifts in microglial metabolic pathways over the course of stroke. ImmunoMet will also evaluate the effects of an acute manipulation of microglia cellular metabolism on the stroke recovery, as an approach to tackle chronic neuroinflammation and improve brain functional recovery after stroke. To this end, ImmunoMet aims to assess microglia immunophenotype in two scenarios: (1) a transgenic mouse line with altered microglia type I IFN signaling, which may regulate energy metabolism, and (2) after administering an itaconate derivate, a modulator of immune cell polarization. ImmunoMet is expected to contribute novel and valuable insights into the immunometabolic adaptations to stroke. This research will be a crucial for future development of therapies aimed at enhancing the long-term recovery of stroke survivors, addressing a significant socio-healthcare challenge. ImmunoMet will be a major step in my academic career as an international independent researcher.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution

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€ 165 312,96
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
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Research Organisations
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