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Deciphering the Transcriptional Logic of TFEB activation in cell identity and cancer

Objective

The discovery that lysosomal biogenesis is subjected to a global transcriptional control and that the transcription factor TFEB is the primary driving force for the coordinated expression of lysosomal genes has empowered intense investigations on the molecular mechanisms regulating cellular homeostasis. Modulation of TFEB expression and activity is therefore crucial in cellular adaptation to a wide variety of internal stresses and environmental fluctuations. While many studies have been focused on TFEB post-translational modifications and on how they can affect its subcellular localization and function, little attention has been given to how TFEB expression is regulated at the transcriptional level across different cell types and nutritional states hampering the capacity of fully benefit from its powerful properties.
By using genomic approaches and induced-pluripotent stem cell-based systems, I aim to define the regulatory architecture of TFEB activation across a broad range of cellular contexts. This will allow understanding how different regulatory mechanisms result in a cell-selective ability to preserve homeostasis and respond to various stress conditions. Specifically, I will: i) define the cell-specific dynamics of TFEB expression; ii) expose novel TFEB transcriptional regulators; iii) identify the transcriptional mechanisms underlying aberrant TFEB activation in cancer. The proposed project will be essential to define the transcriptional landscape of TFEB and will also provide a novel and yet unexplored angle to revise its contribution in disease settings where the lysosome function is impaired.

Fields of science (EuroSciVoc)

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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)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

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.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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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

FONDAZIONE TELETHON ETS
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 VARESE 16/B
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
Links
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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