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A Multi-omics Approach To Decode Epigenetic Lesions In Pancreatic Cancer Development

Project description

Role of epigenetic mutations in pancreatic cancer

Chromatin is a macromolecule that consists of DNA wrapped around histone proteins, enabling transcription factors, signalling pathways and mechanical stimulations to regulate gene expression. Epigenetic mechanisms that alter phenotypes without modifying the DNA sequence allow reversible changes in gene regulation. These aberrations in chromatin regulation are associated with a wide range of diseases, including cancer. The EU-funded MultiPan project aims to study epigenetic mutations in pancreatic cancer, a deadly disease with a poor prognosis projected to become the second most common cause of cancer-related deaths in the next decade. This project will provide a comprehensive investigation of the epigenetic lesions occurring during cancer development and the mechanisms of underlying gene deregulation.

Objective

Chromatin, the complex structured macromolecule consisting of DNA wrapped around histones, represents the ground where transcription factors, signalling pathways and mechanical stimulations converge to regulate gene expression and determine cellular phenotypes. Epigenetic mechanisms altering these phenotypes without modifying the DNA sequence are extremely pliable and allow for subtle and reversible changes in gene regulation. Consequently, aberrations in chromatin regulation are associated with a wide range of diseases, such as cancer, where they can be pivotal for the fitness and activity of malignant cells.
Here we aim to investigate the role played by epigenetic mutations in pancreatic cancer, a dismal disease with poor prognosis and projected to be the second most common cause of cancer-related death in the next decade. The candidate will apply cutting-edge technologies such as parallel single-cell RNA-seq and single-nucleus ATAC-seq to uncover the correlation between changes in chromatin accessibility and gene expression in patient-derived and engineered 3D organoid models. These findings will constitute the basis for functional validations that will involve the combination of epigenomic tools (dCas9-mediated epigenetic modifications) and high-resolution imaging approaches (light-sheet microscopy). Therefore, this project will provide a comprehensive view of the epigenetic lesions occurring during cancer development, shedding light on mechanisms of gene de-regulation and paving the way to novel approaches to cancer treatment.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
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.

€ 162 806,40
Address
Chariteplatz 1
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
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.

€ 162 806,40
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