
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
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.

Chromatin structure
Inflammatory Response | Force Transmission & Sensing
Biomechanics influences gene regulation via chromatin organisation.
In collaboration with subproject P09
Team
Shear-stress dependent modulation of BMP-induced transcription

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

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

Publications
- Authors:Mendez, P. L.; Obendorf, L.; Jatzlau, J.; Burdzinski, W.; Reichenbach, M.; Nageswaran, V.; Haghikia, A., Stangl, V.; Hiepen, C.; Knaus, P.
Journal:BMC Biol Year:2022; Volume:20Issue:(1):Pages:210.
Title:Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes - Authors:Jatzlau, J.; Mendez, P.M.; Altay, A.; Raaz, L.; Zhang, Y.; Mähr, S.; Sesver, A.; Reichenbach, M.; Mundlos, S.; Vingron, M.; Knaus, P.
Journal:iScience Year:2023;
Title:Fluid Shear Stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription