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Exploring the Mechanobiology of the Secretory pathway across scales

Project description

Uncovering the secretory pathway’s mechanisms

Although the secretory pathway is well-studied in 2D cultures, less is known about how it responds to physical and environmental forces. Understanding these complex mechanisms and their role in cellular function and pathogenesis could lead to future treatments for diseases such as colorectal cancer. Supported by the Marie Skłodowska-Curie Actions programme, the MechanoSecret project will study how the Golgi complex, which is at the core of the secretory pathway, responds to external mechanical forces. By investigating the fundamental biology of secretory pathway mechanotransduction in 2D cells, it aims to identify how Golgi dynamics are affected by mechanical forces. Using single-particle tracking in 3D imaging, it will also examine colorectal cancer patient-derived organoids to detect changes in secretion under mechanostimulation.

Objective

Membrane trafficking is fundamental to cellular homeostasis, controlling essential processes ranging from signalling to adaptation to the environment. By regulating secretion, eukaryotic cells modulate plasma membrane composition and the extracellular matrix. Human cells are typically embedded in tissues and constantly experience external forces. While the molecular details of the secretory pathway are well-established in 2D cultures, their response to mechanical cues remains largely unexplored.

This project aims to fill this knowledge gap by investigating how the Golgi complex, the central hub of the secretory pathway, responds to external mechanical forces. Using cutting-edge microscopy, biomaterials, and advanced cell biology, our study will adopt a bottom-up approach. First, we will explore the fundamental biology of the secretory pathway mechanotransduction in 2D polarized and non-polarized cells. Employing super-resolution microscopy and single-particle tracking, we will analyse how external mechanical forces influence Golgi dynamics with unprecedented spatiotemporal resolution. Our second aim extends this research to 3D systems, hypothesizing that inherent forces in these environments affect the secretory pathway. By leveraging colorectal cancer patient-derived organoids, we aim to uncover changes in secretion under mechanostimulation. This project will pioneer single-particle tracking in 3D imaging, integrating expertise from cell biology, optics, and photonics—a synergy uniquely supported by the host institution.

Colorectal cancer, a prevalent and deadly malignancy, suffers from limited therapeutic options due to cellular heterogeneity. By bridging cell biology and biophysics with cancer research, this project holds the potential to identify novel vulnerabilities in colorectal cancer. This study will not only provide fundamental insights into the secretory pathway but also lay the groundwork for future therapeutic strategies against colorectal cancer.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

FUNDACIO INSTITUT DE CIENCIES FOTONIQUES
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.

€ 194 074,56
Address
AVINGUDA CARL FRIEDRICH GAUSS 3
08860 Castelldefels
Spain

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Region
Este Cataluña Barcelona
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Research Organisations
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