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Neutrophil Extracellular Traps Induced Glial Type I Interferon in the Pathogenesis of Tauopathy

Project description

Uncovering the role of neutrophils in neurodegeneration

Neutrophils are primarily responsible for combating infections and mediating inflammatory responses. To capture and kill microorganisms, neutrophils release web-like structures that consist of DNA and antimicrobial proteins called neutrophil extracellular traps (NETs). This same mechanism can also contribute to the development and progression of inflammatory diseases. However, the involvement of NETs in neurodegenerative disorders remains largely unexplored. With the support of the Marie Skłodowska-Curie Actions programme, the TNT project will investigate how NETs contribute to neurodegenerative conditions characterised by abnormal Tau protein accumulation in the brain. Researchers will use animal models and post-mortem human brain tissue to reveal new mechanisms of neuroinflammation and uncover potential therapeutic strategies targeting neutrophil-driven processes.

Objective

Tauopathies, including Alzheimer’s Disease (AD), characterized by the brain accumulation of abnormal Tau proteins, represent a significant unmet medical need. Neuroinflammation is a hallmark of these diseases. Although several neuroimmune regulations, notably involving microglia, have been largely studied recently, the role of neutrophils and the release of neutrophil extracellular traps (NETs) has been overlooked. The TNT project will fill the gap as aimed to (1) characterize the temporal dynamics of neutrophil and NETs involvement vs. Tauopathy progression and (2) evaluate the functional impact of NETs and type I interferon (IFN-I) on disease pathogenesis. Using a combination of approaches, including Tauopathy and Tau seeding models together with post-mortem tissue of patients with primary Tauopathy, the TNT project will advance our understanding of the complex interplay between NETs, glial and Tau pathology, potentially leading to novel therapeutic strategies. The project will study the influence of the biological sex on these mechanisms and assess their therapeutic potential.

The host institute provides a robust platform for bidirectional knowledge exchange, with expertise in Tau transgenic and seeding models, 3D glial cell reconstitution, and inflammasome-Tau pathology, significantly enhancing our research on glial cell changes. My expertise in neuroimmunology and neutrophil biology, will be instrumental in advancing ongoing projects at the host lab. The planned training will enhance my research skills while fostering independence, mentorship, and communication abilities, preparing me for leadership. Engaging in mentorship activities and workshops will equip me with skills to guide and inspire junior researchers, and enhance my ability to communicate complex concepts to diverse audiences. This development will position me as a young leader in neurodegenerative diseases, ready to make significant contributions to scientific advancement and knowledge transfer.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITE DE LILLE
Net EU contribution
€ 242 260,56
Address
42 RUE PAUL DUEZ
59000 Lille
France
Region
Hauts-de-France Nord-Pas de Calais Nord
Activity type
Higher or Secondary Education Establishments
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Total cost
No data

Partners (1)