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

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

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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Coordinator

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Address

Chariteplatz 1
10117 Berlin

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 162 806,40

Project information

Grant agreement ID: 841755

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 162 806,40

  • EU contribution

    € 162 806,40

Coordinated by:

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany