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Macrophage metabolism and signal-induced chromatin and transcription changes: an integrated, multi-layer approach

Objective

Organismal responses to environmental threats involve the activation of both resident and monocyte-derived macrophages, key components of the innate immune system. Macrophages are capable of rapidly sensing micro-environmental changes and of reacting with distinct activities ranging from specialised homeostatic functions, to the activation of effector functions in tissue immune surveillance. These diverse biological outcomes are brought about by the coordinated rewiring of both metabolic and transcriptional networks. Although much is known about the metabolic configuration and the transcriptional signatures of activated macrophages, their reciprocal influences have not been systematically investigated. Metabolic changes linked to acute activation are primarily, although not exclusively, driven by transcriptional changes; nevertheless, how these changes are coordinated and implemented over time remains unsolved. In addition, changes in metabolic state are accompanied by changes in metabolites availability, some of which are cofactors or co-substrates of chromatin-modifying enzymes, essential players in the control of gene expression. I aim to unravel key mechanistic principles on the interplay between transcriptional and metabolic control in macrophages by adopting two complementary approaches: (1) I will identify the complement of transcription factors controlling dynamic metabolic changes at different times during macrophage activation by combining genomic and metabolomic techniques; (2) I will characterise how metabolic pathways signal to specific enhancers thus eventually affecting inflammatory gene transcription and chromatin changes. This project will contribute to systematically dissect fundamental principles of integrated cell control in response to micro-environmental stimuli, advancing our understanding of the coordination between metabolic re-programming and gene transcriptional programs.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

UNIVERSITA HUMANITAS
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.

€ 180 277,20
Address
VIA RITA LEVI MONTALCINI 2/4
20072 PIEVE EMANUELE
Italy

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Region
Nord-Ovest Lombardia Milano
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.

€ 180 277,20
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