Project description
Melanocortin 3 receptor and muscle atrophy body composition
Muscle loss, or muscle atrophy, is associated with inactivity, ageing and malnutrition, as well as diseases like cancer cachexia, where muscle wasting increases mortality risk. Although we do not fully know how the body regulates muscle mass in response to nutrient sensing, growing evidence suggests the understudied melanocortin 3 receptor (MC3R) may control body composition and lean mass. With the support of the Marie Skłodowska-Curie Actions programme, the IMMAc project will investigate the mechanisms that control muscle mass and body composition and demonstrate the role MC3R plays during adulthood. It will also explore the potential for manipulating MC3R to treat muscle atrophy and obesity by increasing lean mass in cachexia and by improving anti-obesity agents through preventing functional muscle loss.
Objective
We are yet to understand how the body regulates muscle mass in response to nutrient sensing at a whole organism level. The loss of muscle mass occurs in a range of diseases, including cancer cachexia, in which mortality risk is substantially increased by muscle wasting. The melanocortin signalling system in the hypothalamus is a crucial node in energy and nutrient sensing, with growing evidence implicating the understudied melanocortin 3 receptor (MC3R) in the control of body composition and lean mass. To date, the influence of MC3R tone on muscle mass has only been studied in mice and humans lacking MC3R from conception. To understand MC3R action and the spatial and temporal relevance of the receptor in regulating muscle mass, using in vivo and ex vivo approaches, IMMAc will:
7. Determine the neuroendocrine effects of MC3R activity
8. Assess the role of a putatively critical MC3R sub-population in controlling body composition and muscle mass
9. Determine the importance of MC3R for muscle mass in a mature organism and the extent to which MC3R tone can be manipulated to therapeutically alter muscle mass in adulthood
Neuroendocrine impacts of MC3R activation will be examined using ex vivo hypothalamic culture and in vivo. Neuron-specific deletion of MC3R will allow mechanistic understanding of MC3R action, and the physiological and functional consequences of MC3R activation on skeletal muscle will be assessed by examining physical activity and fibre functionality.
IMMAc will provide understanding of mechanisms underlying control of muscle mass and body composition by a key central nervous system receptor. Moreover, this project will reveal the relevance of MC3R for muscle mass in adult life and explore the therapeutic potential of manipulating MC3R to address the global health challenges of muscle atrophy and obesity by increasing lean mass in cachexia and improving increasingly prevalent anti-obesity agents through preventing loss of functional muscle.
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.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine oncology
- medical and health sciences health sciences nutrition obesity
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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.1.2 - 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.
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.
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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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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.
CB2 1TN CAMBRIDGE
United Kingdom
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