Nos tutelles


   

   

nos reseaux sociaux


               

Rechercher




Accueil > Équipes > OPTique et IMAgeries > Physique et Imagerie pour le vivant > Dynamique et signalisation cellulaire

Dynamique et signalisation cellulaire

publié le , mis à jour le

PIs : M. CANEPARI, Antoine DELON, Aurélie DUPONT
Technical Support : S. Costrel, P. Moreau

Part of the team is interested in tackling basic biological questions with multi-disciplinary approaches. They develop and apply novel technical and/or methodological tools to understand how cells function. Namely, development in FRET quantification and fast calcium imaging allow the precise measurement of intracellular signal processing (FRET-based biosensors) and intercellular signaling in the context of neuronal ion channels ; while Fluorescence Fluctuation microscopy approaches allow interrogating the mobility and aggregation state of proteins in living cells and improve the quality of thick tissue imaging.


1 Mechanical signal processing at the cell scale - Aurélie Dupont

2 Integrated Technologies to Study the Physiological Synergy of Neuronal Ion Channels - Marco CANEPARI

3 Fluorescence Fluctuation Microscopy application to cells, tissues and some optical challenges - Antoine DELON


1 Mechanical signal processing at the cell scale - Aurélie Dupont

CellSignalDynamics

Cells can sense the physical properties of their environment through a mechanism called mechanotransduction and accordingly modulate essential functions such as motility, adhesion or differentiation. Molecular interactions are now well described, showing very complex networks, however the coordination in space and time of mechanical and biochemical signals is not yet clear.

The main goal is to understand this mechano-chemical coupling at the scale of an individual cell with an experimental approach. In order to be able to mechanically stimulate a living cell and simultaneously read its biochemical response, with a good spatio-temporal resolution (1µm , 0.1s), we have developed innovative methods : unique activable substrates[1] and a quantitative method[2] of measuring Fluorescent-Resonance-Energy-Transfer (FRET) based biosensors. On-going work aims at measuring the spatio-temporal response function of key signaling proteins after a defined mechanical perturbation. The ultimate goal is to understand how cells process information, especially mechanical information. This interdisciplinary project is supported by collaborations with biologists from Grenoble (O. Destaing & C. Albiges-Rizo, IAB ; U. Schlattner, LBFA) and soft matter biophysicists (J. Rädler & E. Frey, LMU, Munich).

Beyond mechanotransduction, we are interested in the interactions between living organisms and their physical environment in a more general way. A new project is starting to understand how collective effects in small fish are impacted by the environment (obtacle, flow).

Read more.

[1] "Magneto-active substrates for local mechanical stimulation of living cells". Bidan et al. Scientific Reports 8 (1), 1-13 (2018)
[2] "QuanTI-FRET : a framework for quantitative FRET measurements in living cells". Coullomb et al. Scientific Reports 10 (1), 1-11 (2020)


2 Integrated Technologies to Study the Physiological Synergy of Neuronal Ion Channels - Marco CANEPARI

CellSignalDynamics

The group of M. Canepari is member of the Labex Ion Channel Science and Therapeutics (ICST, http://www.labex-icst.fr/en), recently renewed until the end of 2024. Within the consortium mission, the group develops original methods to optically record the physiological activity of ion channels. The aim is to record the cell signaling pathways originating from ion channels, which constitute the most important super-family of transmembrane proteins. The goal is to extend recently developed methods to record Ca 2+ channel activity to Na + channel activity using recent Na+ probes. Hence, Na+ and Ca2+ fast optical recordings can be combined together and/or with Vm imaging or photostimulation to understand the functional interaction among different ion channels. Novel funding of ICST will be devoted to this research line by supporting two PhD scholarships (2019-2022 and 2021-2024). The necessary use of animal models is done by partnership with the Inserm Laboratory LBFA (U1055).


3 Fluorescence Fluctuation Microscopy application to cells, tissues and some optical challenges - Antoine DELON


CellSignalDynamics

Cell response at the molecular scale can be probed using fluorescence fluctuations microscopy (FFM), a family of methods derived from fluorescence correlation spectroscopy (FCS). These methods exploit the statistical properties of detected fluorescence, in single points or images, to obtain information about molecular mobility and aggregation state. In collaboration with biologists (O. Destaing, IAB, Grenoble), the group works on optogenetic systems (molecular interactions that are activated by light) : for example, optogenetics can be used to activate different cell response by modulating the oligomerization state of signaling molecules that can be quantified by FFM. Fluctuation-based techniques also led to the emergence of a technology-transfer project, ConfoBright, coordinated by A. Delon. It aims at supporting innovation for cancer research at IAB. This unique instrument combines a confocal microscope, a customized AO system and a 2-photon laser. We will develop multi-metric strategies, where spatial properties such as contrast or intensity (i.e. image metrics) are combined with local measurements (i.e. fluctuation metrics), that can be tailored to answer specific biological questions. Various projects at IAB will benefit from the ConfoBright system : profound imaging in cell spheroids, 3D assessment of macrophages phagocytosis of cancerous cells, chromatin organization, nuclear shape and cancer, ultra-fast 3D confocal imaging of rapid calcium events.