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HUNTING GHOST NEURONS IN THE NEUROENDOCRINE HYPOTHALAMUS

Objective

The hypothalamus contains heterogeneous neurons that dictate behaviours and physiological functions through cross-talk mechanisms with peripheral hormones. Neuronal diversity is the key to enabling hypothalamic functions and, according to the neuroscience dogma, is mainly preset during embryonic life. But what if this model is incorrect? Can neuronal heterogeneity be plastically modulated throughout adult life as well? Here, based on my published work and solid preliminary results, I propose that special 'Ghost' neurons in the hypothalamus display plastic mechanisms of cell-identity reprogramming to accommodate neuroendocrine functions in adult life under physiological conditions. Such identity plasticity can become maladaptive and contribute to neuroendocrine disorders such as obesity. My central hypothesis is that atypical 'Ghost' neurons are hidden within mature populations of neuroendocrine brain neurons. The Ghostbuster project will hunt down these brain cells and uncover their role in physiology and metabolic disease. A multidisciplinary approach will be used toward this goal, uniting lineage tracing strategies, nutritional interventions, single-cell profiling of hypothalamic neurons, bioinformatic analyses, and viral-based tools for targeting Ghost cell-related genes. These strategies will be combined with behavioural, metabolic and hormonal assessments of mice models of Ghost neuron loss or gain of function. The project will overturn the dogma that post-mitotic neurons have negligible cell-reprogramming capacity and revolutionise our understanding of how brain functions are plastically regulated throughout life. We will shed light on key molecular targets that allow the reprogramming of neuronal functional identity for therapeutic use and provide a novel framework for understanding the fundamental biological mechanisms that cause neuroendocrine disorders such as obesity, infertility, and beyond.

Fields of science (EuroSciVoc)

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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)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

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.

Funding Scheme

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

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-COG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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