Objective
New anti-obesity drugs targeting incretin receptors (IRAs) offer the first safe and effective anti-obesity treatments. However, their long-term benefit is limited by high discontinuation rates due to major intestinal side effects. IRAs suppress appetite by signalling in the brain, but due to their large size, they only access aversive circuits of the hindbrain and fail to diffuse to hindbrain regions supporting non-aversive satiety. Access to these deeper regions is restricted by the Funiculus Separens (FS), a poorly characterised diffusion barrier. I hypothesise that the FS gates diffusion of IRAs to deeper hindbrain regions and determines whether IRAs recruit aversive rather than non-aversive appetite-suppressing circuits.
I will use an interdisciplinary multi-omics approach to deliver the first molecular, cellular, structural and functional map of the FS. I will test how obesity and IRAs remodel FS structure and function, integrating behaviour, in vivo recordings, and whole-brain c-Fos mapping in lean and diet-induced obese mice. Finally, I will establish causality between FS function and behavioural responses to IRAs. For this project, I bring expertise in the gut–brain axis, glial and brainstem neurobiology, brain surgery and behavioural phenotyping. The host institution will provide state-of-the-art core facilities (genomics, imaging, proteomics, neurotechnology), supervision in nutrient sensing, IRA mechanisms and ECM biology, and structured training (spatial transcriptomics, proteomics, image analysis, tissue clearing, fibre photometry, leadership). The project will produce open, reusable assets (standard operating procedures, analysis code, datasets) and advance multi-omics and multiplexed 3D imaging in metabolic neuroscience. Longer term, the framework extends to other circulating peptides with aversive components, informing better-tolerated therapies and enabling cross-disciplinary links with oncology/cachexia, maternal health, and gastroenterology.
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 neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine surgery
- medical and health sciences health sciences nutrition obesity
- medical and health sciences clinical medicine gastroenterology
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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)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-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-2025-PF
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CB2 1TN CAMBRIDGE
United Kingdom
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