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ChroMet

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Elucidating the role of macroH2A1.2 histone variant as a metabolic sensor in the...

Elucidating the role of macroH2A1.2 histone variant as a metabolic sensor in the epigenetic regulation of leukaemia cell fate. The initiation and maintenance of leukaemia are often regulated through the interaction of epigenetic mechanisms and metabolism, but how these affect each other, is not always fully understood. One of the epigenetic mechanisms tha... ver más

31/07/2026

FUNDACIO INSTITUT...

165K€

Presupuesto del proyecto: 165K€

Líder del proyecto

FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEM... Actividades de investigación asociacion

TRL 4-5 | 50K€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-03-21

HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022 ExpectedOutcome:

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1 Participantes

FUNDACIO INSTITUT DE RECERCA...

165.31K€ | Lider

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Duración del proyecto: 40 meses Fecha Inicio: 2023-03-21
Fecha Fin: 2026-07-31

Líder del proyecto

FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEM... Actividades de investigación asociacion

TRL 4-5 | 50K€

Presupuesto del proyecto 165K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The initiation and maintenance of leukaemia are often regulated through the interaction of epigenetic mechanisms and metabolism, but how these affect each other, is not always fully understood. One of the epigenetic mechanisms that alter cell fate is the replacement of replication-coupled histones with non-canonical variants. MacroH2A (mH2A) variants (mH2A1.1, mH2A1.2 and mH2A2) have a large, metabolite-binding macrodomain and differ from each other solely in the structure of their ligand-binding pocket. Of those three, only mH2A1.1 has known ligands, while the binding partner and corresponding biological functions of mH2A1.2, are still unknown. The preliminary data suggest phospholipid molecules as unique ligands of mH2A1.2. At the same time, they show that the MACROH2A1 is required for the maintenance of the stemness of leukaemia stem cells and leukaemia itself. During the ChroMet project, by using cutting-edge techniques in cell and molecular biology, computational biology and biochemistry, I aim i) to confirm the identity of putative ligands of mH2A1.2 and to biophysically characterize the binding interaction, and ii) to test the contribution of the newly identified metabolite-binding capacity of mH2A1.2 on the leukemia cell differentiation and tumorigenicity. The findings of the project will allow me to describe the mH2A1.2 as an entirely novel metabolic sensor on chromatin, which, through the binding of phospholipid ligands, regulates cell metabolism and impacts leukaemia cell fate. The complementary knowledge and expertise of the hosting group (in epigenetics and metabolism), the hosting institute and long-standing collaborators (in leukemia research), and my own (in biochemical analyses of protein-ligand interactions) will ensure the successful realization of the proposed project and contribute to the development of my career as an independent researcher, committed to exploring an interplay between epigenetics, metabolism and cancer.

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