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DFG Collaborative Research Centre 1444

This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.

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Subproject 4 - Principal Investgators

Prof. Dr. Petra Knaus

CRC 1444 Representative of partner university & Education of early career scientists, Subprojects 3 & 4 | RU 2165 Subprojects 3

The effects of mechano-biology on chromatin folding and gene regulation

Knaus and Mundlos analyse the effects of mechanical stimuli, which are so essential for bone healing, on chromatin folding and gene regulation. They hypothesise that mechanical forces influence gene expression via re-positioning of the chromatin in the three-dimensional space of the nucleus. Alterations of the extracellular matrix composition, the fluid shear stress and other external forces might therefore modulate gene transcription during disease and tissue regeneration. Preliminary data with endothelial cells shows striking changes in cellular mechanics, nuclear lamina and extracellular matrix composition, as well as increased F-actin bundling and tubulin acetylation, resulting in increased cellular tension and nuclear deformation. Knaus and Mundlos characterise the nuclear modifications, identify lamina associated domains and perform chromosome conformation capture to characterise the nuclear three-dimensional organisation upon mechanical stimulation.

Most important results

Mechano-responsive transcription factors

Inflammatory Response | Force Transmission & Sensing

BMP9-induced SMAD transcriptional response is modulated by blood flow.

Jatzlau et al. iScience 2023

Aberrant blood flow

Inflammatory Response | Force Transmission & Sensing

Changes in blood flow influence growth factor signalling and consequently inflammatory processes.

Mendez et al. BMC Biol 2022

Chromatin structure

Inflammatory Response | Force Transmission & Sensing

Biomechanics influences gene regulation via chromatin organisation.

In collaboration with subproject P09

Team

Jerome Jatzlau (Postdoc)

Shear-stress dependent modulation of BMP-induced transcription

Paul-Lennard Mendez (Doctoral Researcher)

Understanding the molecular and genetic basis of vascular diseases using in-vitro models

© David Ausserhofer
Lion Raaz (Doctoral Researcher)

Chromatin organization and gene regulation under physical forces of fluid shear stress in the vascular system

© David Ausserhofer

Publications


 

 

 

 

Founded by the DFG (Project Number: 427826188)
Funding Period 2021-2024