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Mecanotransduction: from cell surface to nucleus

Mecanotransduction: from cell surface to nucleus

By In Aiv Internship On June 6, 2018


Internship title: Mecanotransduction: from cell surface to nucleus

LABORATORY
Name: Institut Jacques Monod
Affiliation: CNRS Université Paris Diderot
Address: 15 rue Helene Brion
E-mail: nicolas.borghi@ijm.fr

LAB Director
Name: Nicolas Borghi
Phone number: +33157278041
E-mail: nicolas.borghi@ijm.fr

SUPERVISOR
Name: Nicolas Borghi
Phone number: +33157278041
E-mail: nicolas.borghi@ijm.fr

Subject Keywords: mechanotransduction, cell adhesion, nucleus, biosensors, microscopy
Tools and methodologies: FRET microscopy, molecular bioengineering, biosensors, super-resolution, single-molecule imaging
Summary of lab’s interests: Cells generate and experience mechanical forces that are propagated throughout the organism. Ultimately, these forces may shape tissues and organs, and regulate genetic programs. The molecular mechanisms of thes processes are poorly understood. We study the macromolecular complexes that transmit and transduce mechanical cues within and between cells, and the cell functions affected by these cues. To do so, we apply and develop genetically encoded biosensors and advanced microscopy and micromanipulation methods to dynamically and quantitatively control and monitor the behavior of protein complexes and cells in a wide range of time- and length-scales in cell culture model systems.
Project summary: The topic of the internship may address:
– mechanotransduction through nuclear envelope complexes and its link with gene expression:
The goal here is to first correlate molecular tension within the LINC complexes and chromatin dynamics and accessibility measured by fluorescence spectroscopy approaches. Second, we will determine how extracellular mechanics affect chromatin dynamics and accessibility and the role of LINC complexes above by adding targeted mechanical, pharmacological and genetic perturbations.
– the mechanical crosstalk between cell adhesion and LINC complexes:
The goal here is to correlate molecular tensions between complexes of cell-cell, cell-matrix adhesion and of the nuclear envelope. Second, we will determine how extracellular mechanics affect these correlations by adding targeted mechanical, pharmacological and genetic perturbations.
– molecular tension spectroscopy in live cells:
The goal here is to combine molecular tension sensors and single molecule imaging to determine the distribution of molecular tensions among the population of proteins of interest and through time.

Interdisciplinary aspect of the project: The project generally targets the understanding of the mechanical properties and behavior of living matter and their impact on biological functions. It combines molecular bioengineering, cell culture, quantitative fluorescence microscopy, single-molecule physics, image analysis and it aims at connecting molecular to cell scales. The project will involve strong interactions with team members with backgrounds spanning from soft matter physics to molecular and cell biology, and microscopy/spectroscopy engineering.