Objective
Metabolic functions in vertebrates are ruled by thyroid hormones, produced by the thyroid gland and secreted into the bloodstream. Thyroid hormone levels modulate growth, development and many other key processes across the lifespan, and their impairment severely affects human health. Despite extensive studies, controlling hormone levels in vivo remains a major challenge. Synthesis of thyroid hormones occurs extracellularly, via iodination of thyroglobulin. They must then undergo endocytosis before they can be released into the bloodstream. Yet, most thyroglobulin forms a colloid matrix within the gland, enabling iodine and hormone storage for the body. How these three mechanisms are balanced to provide physiological levels of hormones to the organism remains an outstanding question. Using an integrative structural biology approach, the proposed research will focus on unravelling the molecular mechanisms underlying the major checkpoints of thyroid hormone synthesis. My research group will combine electron cryo-microscopy with biochemical and light microscopy tools to study thyroid hormone regulation at different scales: from in vitro reconstituted systems to native thyroid organoids. First, we will elucidate how thyroglobulin iodination modulates hormone yields and modifies thyroglobulin structure. Second, we will determine the mechanism of thyroglobulin endocytosis regulated by two main receptors. Third, we will decipher the mechanism of storage and depletion of the thyroglobulin storage matrix. These approaches will allow us to reproduce the complexity of thyroid hormone synthesis at high resolution and in a native environment. My expertise in structural biology and my pioneering work on thyroglobulin puts me in an ideal position to carry out this work. The expected outcome and method development of this research will open a new front in thyroid structural biology and inspire alternative strategies for the control of thyroid hormone synthesis in vivo.
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.
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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)
MAIN PROGRAMME
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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.
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-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-STG
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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.
20157 Milano
Italy
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