Valentin Dunsing-EICHENAUER

Contact
valentin.dunsing 'at' univ-amu.fr
ORCID
google scholar

Biography

Main research interest

I am fascinated how cells collectively self-organize into diverse tissues and organs, which is beautifully exemplified during embryonic development. While this has been extensively studied in model organisms, recent advances in stem cell and organoid technologies now allow us to recapitulate these remarkable processes in vitro and even build functional structures for pharmaceutical and medical applications. 

In my research, I want to understand how cells integrate genetic programs, signaling, mechanics and metabolism to commit to specialized fates, on an individual and collective level. I also aim to understand how emerging cell populations form functional morphological structures such as organs. To this aim, I recapitulate early development using embryonic organoids (currently mouse but soon also human). My current research focuses on the formation of the germ layers and the main body axes. I investigate these questions on multiple levels from the molecular to the cellular and multi-cellular scale.

More information can be found here: Biophysics of embryonic organoids self-organization 

Technical approaches

I build on my strong background in optical microscopy and utilize multimodal 3D imaging techniques (e.g. long-term and high throughput light-sheet, 2-photon, FLIM and quantitative fluorescence fluctuation spectroscopy techniques), biophysical methods and computational analysis (conventional and deep learning) to follow cells on their trajectories from a pluripotent state to a specialized fate. Currently, I also start to integrate these approaches with single cell genomics techniques. 

We develop quantitative imaging pipelines using multi-view 2-photon (top) and single-objective light-sheet microscopy (bottom) to image organoids of several hundred micron size in toto at high throughput (with Alice Gros and Jules Vanaret).

Current projects

Mechanisms of patterning and symmetry breaking in embryonic organoids

The emergence of asymmetries within a mass of equivalent cells is a key event in embryonic development, resulting in formation of the main body axes. We investigate symmetry breaking in gastruloids, an in vitro model of early mammalian embryogenesis. Upon Wnt activation, polarized gene expression patterns emerge from an initially homogenous state, followed by elongation and formation of germlayer-like tissues. Interestingly, robust symmetry breaking occurs only in aggregates of a certain size, smaller or larger aggregates do not polarize. In addition, recent research suggests that gradients of gene expression in gastruloids at an early stage are predictive on the morphogenetic potential at a later stage. To understand these phenomena, we investigate how gene expression patterns arise during Wnt activation.


I use single-objective lightsheet microscopy to acquire long-term movies of gastruloids during symmetry breaking (see example of an 8h movie below) and analyse gene expression patterns, cell movements, deformations, interactions and tissue flows.

Brightfield 

Fluorescence (nuclei)

Time-registered movie

Optic Flow analysis

Development of novel optical approaches

I develop and combine optical microscopy techniques to create new tools to observe highly dynamic living specimen in a quantitative manner. This involves lightsheet and 2-photon microscopy, spectral imaging, fluorescence lifetime imaging microscopy, fluorescence correlation spectroscopy, optical sensors and clearing techniques. 

I collaborate with industrial partners to benefit from the latest technology. Together with the Berlin based photonics company PicoQuant GmbH and Pi Imaging Technologies, we have accelerated FLIM by two orders of magnitude using single-objective light-sheet microscopy.

Fluorescence lifetime multiplexed imaging of embryonic organoids using single-objective light-sheet microscopy (from Dunsing-Eichenauer et al., bioRxiv, 2024)

Morphogen dynamics and instruction of cell fate decisions during embryonic development

How do cells communicate with each other across a tissue? During embryogenesis, cells exploit conserved signaling pathways to instruct cell state transitions and morphogenetic events, for example through diffusible ligands such as morphogens. To monitor morphogen transport and receptor interactions during morphogenesis, I utilize fluorescence fluctuation spectroscopy techniques in vivo, e.g. in C. elegans and Drosophila embryos.

In vivo dynamics of Wnt ligands in C. elegans embryo probed by fluorescence correlation spectroscopy (from Recouvreux et al., Current Biology, 2024)

Publications

Current Biology 34, 1853–1865, https://doi.org/10.1016/j.cub.2024.03.030

Dunsing-Eichenauer, V. #, Hummert, J.#, Chardès, C., Schönau, T., Guignard, L., Galland, R., Grenci, G., Tillmann, M., Koberling, F., Nock, C., Sibarita, JB., Viasnoff, V., Antolovic, IM., Erdmann, R., Lenne, PF. (2024)

bioRxiv 2024.03.24.586451; doi: https://doi.org/10.1101/2024.03.24.586451 #shared first and co-corresponding authors

Nature Communications 14, 5547. https://doi.org/10.1038/s41467-023-41178-w

PLOS ONE 18(8): e0285486. https://doi.org/10.1371/journal.pone.0285486

bioRxiv 2022.09.28.509885; doi: https://doi.org/10.1101/2022.09.28.509885, accepted at Nature Protocols

Biophysical Journal, 2022 Dec 15;S0006-3495(22)03927-3. doi: 10.1016/j.bpj.2022.12.017.

Nature Chemical Biology, 18(1), 64-69

Biophysical Journal, Volume 120, Issue 4, Pages 5478-5490

eLife 2021;10:e69687. #co-corresponding authors

Journal of Biological Chemistry 296 100286

Biomacromolecules 20, 3842-3854.

Journal of Visualized Experiments (142), e58582.

Scientific Reports 8:10634. #shared first authors

Molecular Biology of the Cell 28, 3609-3620.

Journal of Virology 91:e00267-17.

Journal of Neurochemistry, 137: 266-276.

Biophysical Journal, Volume 109, Issue 3, Pages 477-488