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IRON-BETA - Unraveling the iron metabolism of pancreatic β-cells

Objective

Iron is a critical cofactor for proteins and enzymes involved in oxygen and energy metabolism, functions that are especially vital in pancreatic β-cells. In these cells, iron is indispensable for mitochondrial respiration, the process that powers insulin production. However, disruptions in iron homeostasis - whether through deficiency or overload - have been linked to β-cell dysfunction, yet the underlying mechanisms remain poorly understood. With IRON-BETA, I seek to unravel how iron metabolism regulates β-cell identity, function, and survival, under both normal and stressed conditions, such as type 2 diabetes (T2D) and early post-transplant ischemia. Using cutting-edge techniques and models, including multiplex single-cell RNA-Seq, super-resolution microscopy, ICP-mass spectrometry, novel genetic mouse models, and iPSC-islet cell differentiation, I, together with my team, will comprehensively explore the role of iron in β-cell biology. We will map iron distribution in islet cells, particularly β-cells, to understand its impact on their function and overall islet health. We will investigate how fluctuations in iron availability contribute to β-cell dysfunction in T2D, with the aim of identifying novel therapeutic targets. Additionally, we will optimize iron supply during the maturation of iPSC-derived β-cells to enhance their functional capacity for cell-based therapy. Finally, we will explore the interplay between iron and oxygen homeostasis in β-cell grafts, focusing on hypoxia-inducible factor 1-alpha (HIF-1α) signaling—a crucial regulatory pathway that integrates both iron levels and oxygen availability. By evaluating how iron deficiency and hypoxia impact β-cell survival and graft success during islet transplantation, we aim to improve transplantation outcomes and advance therapeutic strategies. By addressing these critical gaps in understanding iron homeostasis, IRON-BETA will open new avenues for treating T2D and advance β-cell replacement therapies for T1D.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-STG

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Host institution

VRIJE UNIVERSITEIT BRUSSEL
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.

€ 1 498 000,00
Address
PLEINLAAN 2
1050 BRUSSEL
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 498 000,00

Beneficiaries (1)

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