Constituent teams: Hadi BOUKHATMI, Romain GIBEAUX, Régis GIET, Roland LE BORGNE, François LEGOUX, Grégoire MICHAUX, Jacques PÉCRÉAUX, Marc TRAMIER, Gwenaël RABUT
Key words: cell division, cell cycle, cell polarity, microtubules, mitotic spindle, mitochondria
From the simplest to the most complex eukaryotes, cells are the building blocks of life. The teams that participate in this axis explore the fundamental mechanisms that control the dynamics of cell properties at different scales ranging from biochemical networks and subcellular elements to cells and tissues. The aim is to understand how cells modulate their organizations, sizes, shapes, and numbers in response to internal and external biochemical or mechanical cues. We also study the plasticity of cellular and developmental events, focusing in particular on biophysical and evolutionary constraints that impose predetermined yet flexible fates. We use both top-down and bottom-up approaches to understanding the roles of molecular mechanisms in building cells and tissues, as well as for investigating how tissue and cellular parameters influence molecular mechanisms.
The various teams in this grouping will explore the biochemical and mechanical regulations of cellular processes, with a special emphasis on cell division and the cell cycle. In this context, we will examine the functions of biophysical parameters (LE BORGNE and PECREAUX teams); the impact of microtubule structure and dynamics on cell division (GIBEAUX, GIET, and PECREAUX); terminal differentiation (MICHAUX); and the control of mitochondrial functions (TRAMIER). We will also investigate the maintenance of cell polarity and tissue integrity in proliferative epithelia (LE BORGNE), and the formation and maintenance of the intestinal brush border (MICHAUX). Finally, we will take automated and large-scale approaches to the quantification of molecular interactions and cell functions (RABUT and TRAMIER).
We predict that the sizes and shapes of individual tissues or cells play major regulatory roles at all scales, all the while influencing how cells adapt and evolve in a variety of conditions. We therefore aim at establishing these parameters as essential regulators of cell and tissue behaviours. For instance, at the cellular level, we will investigate how microtubule networks (such as the mitotic spindle) adapt their morphologies and accommodate to the geometry and size of different cells (GIBEAUX, GIET, and PÉCRÉAUX). At the tissue level, we will examine how tissues adapt to overproliferation in a constrained environment (MICHAUX).
To pursue these lines of research, we will work with a broad range of model organisms, including budding yeast (RABUT), Caenorhabditis elegans (MICHAUX and PECREAUX), Drosophila (GIET and LE BORGNE), and Xenopus (GIBEAUX), as well as with ex vivo organoid models (LE BORGNE and MICHAUX). We thus adopt multiscale quantitative strategies, taking advantage of state-of-the-art genetic tools, systematic protein interaction mapping, and cutting-edge microscopy. Our imaging expertise integrates a strong know-how of the monitoring of spatiotemporal regulation and diffusion of molecular complexes, photo manipulation, and molecular and cellular electron tomography methods. Furthermore, we will develop new advanced systems that allow for fast live-cell super-resolution and deep learning-based autonomous microscopy. Finally, data analysis using bioinformatic tools will be developed in coordination with the GBC group to help the IGDR make use of mid- and high-throughput results.
The mechanisms we are exploring are all essential, enabling the correct functioning of cells, tissues, and organisms. Their misregulation can trigger the emergence of pathological situations such as cancer or genetic and orphan diseases. Our unique multi-disciplinary and multi-model approaches put us in an ideal position to tackle fundamental questions and then to complete them by addressing the physiological and clinical relevance of our discoveries.
These two large research axes will be supported by weekly internal meetings.