Project description
Microglia role in brain development and metabolism control
Recent evidence demonstrated that, besides representing the first residential immune line of defence against pathogens, microglia are involved in the development and physiological functions of the central nervous system. They affect neuronal apoptosis, neurogenesis and myelin formation and manage synapse development and homeostasis. Triggering receptor expressed on myeloid cells-2 (Trem2) has emerged as a key regulator of microglial metabolism, in addition to directing synapse elimination and functional brain connectivity. The EU-funded MATILDA project will study how microglia, via Trem2, direct brain developmental patterns. Project data will specifically elucidate the role of microglia in the regulation of hypothalamic complexity and endocrine output.
Objective
Microglia represent the main brain residential immune cells. In the last years evidence emerged that, besides representing the first line of defense against pathogenic insults, microglia are also centrally involved in physiological functions essential for correct CNS development and function. Microglia, in a spatially and temporally controlled manner, influence neuronal apoptosis, neurogenesis and myelin formation and manage synapse homeostasis, including removing supernumerary synapses during development. These widely heterogeneous roles are supported by distinct subtypes -or states- of microglia, present in different regions of the brain and at different times during CNS development. In the last years, Triggering Receptor Expressed on Myeloid cells 2 (Trem2) emerged as a key gene which controls the microglial metabolic state, in addition to directing synapse elimination and shaping the functional brain connectivity. In the present project, I propose that microglia, via Trem2, direct the genetic signature of specific subgroups of brain cells, shifting them toward specific metabolic and developmental patterns. I hypothesize that this mechanism is key for the control of metabolism in the hypothalamus, where the neuronal contingents orchestrating systemic energy homeostasis reside. By using a combination of transcriptomics, multiplex protein expression analysis and cell-based imaging methods, I will determine which subsets of microglia cooperate within hypothalamic centers and will define the underlying mechanisms. I will also assess whether defects in this orchestrated crosstalk affect the central regulation of energy and glucose homeostasis during aging. Data from this study will provide comprehensive knowledge of microglia functions in shaping hypothalamic complexity and endocrine output. Also, they will offer a targeting potential for new therapeutic strategies that could reverse immunometabolic dysfunction by modulation of hypothalamic microglial function.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-ADG
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20100 Rozzano (Mi)
Italy
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