Research

 

 

 

 

The spatial organization of cells is key to regulate many fundamental biological processes, including, cell migration, division, embryo development and tissue repair. Defects in cellular organization are often associated with the emergence of developmental defects, and severe diseases like cancer.

Our team aims to understand the basis of cellular organization, by addressing questions including: How do cells determine their functional morphologies? How might they probe their own size and shape? How do these geometrical properties contribute to regulate cell division, growth and tissue architecture?

To reach these goals we combine expertise from different fields including chemistry, biology and physics. We integrate and develop state of the art quantitative approaches, such as micro-fabrication, mathematical modeling and image analysis tools, with more traditional genetics and biochemistry approaches. We aim to establish quantitative rules that regulate morphogenesis in unicellular and multicellular organisms.

 

Cells come with stereotypical shapes and sizes which are often associated with their function. Neurons grow in highly elongated morphologies to build neuronal networks, while red blood cells have discoid-like deformable morphologies to squeeze within tiny blood vessels. Questions that fascinate our team are to understand how cells define their particular shape, and how information in cell geometry may be conveyed into cell function or in organizing the cell interior. To address these fundamental questions, we integrate original methods at the frontier between molecular biology, genetics and physics and mathematics. One of our ultimate goal is to capture biological behavior with mathematical models. The current main research area of our team include:

 

1-      Division plane positioning and early embryo development. 

 

The proper positioning of the site of cell division is crucial not only for the survival of all cells, but also for the development of multi-cellular tissues. The lab is fascinated by the process of early embryogenesis during which the egg becomes fertilized and follows a stereotypical choreography of successive division, called cleavage patterns. Our goal is to understand, predict and establish quantitative laws that explain the patterning of cell divisions in early embryos. To this end, we combine mathematical modelling, imaging and biophysics approaches (Figure 1). Our model experimental system is the sea urchin embryo, which integrates many advantages for the study of early development. To extend our findings to other multicellular embryos and tissues, we also have collaboration with other labs, working on flies, frogs, fishes and ascidians, as well as organoids.

 

Figure 1: A. In sea urchin zygotes, like in many cells, microtubule asters allow to probe cell shape to orient the nucleus and the subsequent division axis with respect to cell shape (Minc et al. 2011). B. Use of magnetic tweezers to apply forces on mitotic spindles in intact cells, and to control division plane orientation (Xie et al. 2021). C. Numerical simulation of the forces exerted by microtubules to center the nucleus at fertilization (Tanimoto et al. 2016). D. Simulation of the successive division geometries that mark the cleavage stage of early sea urchin embryos (Pierre et al. 2016).

Video1

Legend : Developping sea urchin embryos where DNA is labelled with a fluorescent dye.

 

Funding: La Ligue Contre le Cancer ; Fondation Bettencourt-Schueller ; European Research Council ; Mairie De Paris; Fondation de la Recherche Médicale

Collaborations: Guillaume Romet-Lemonne (IJM) ; Delphine Delacour (IJM) ; Aki Kimura (NIG, Japan) ; Yohanns Bellaiche (Institut Curie, Paris) ; CP Heisenberg (IST austria) ; Martin Wühr (Princeton University) ; Dan Levy (U. Wyoming).

Key words: Cell division, Cytoskeleton, Morphogenesis, Embryo development.

 

2- Cell shape and polarity 

 

The morphology of single cells as well as cells embedded in tissues underlie many of their function. We seek to address how cells develop their particular shape and internal organization. For instance, many cells only grow at a given location, a process called polarized growth, which involves specific biochemical reactions needed to cluster a local domain of growth activity (Vidéo 2). To study these aspects we use a unicellular fungi called fission yeast. These cells have rod-shapes and are genetically tractable, with many mutants defective in morphogenesis. These cells are encased in a stiff cell wall and are turgid, which provides them with particular mechanical properties (Figure 2). One of our ultimate goal is to link biochemical and biomechanical signals which serve to shape cells.

 

Figure 2: A. Fluorescent images of yeast cells expressing fluorescent proteins to visualize the cytoskeleton, polarity, growth and cell division (Bonazzi et al. 2015). B. Super-resolution images of cell wall thickness dynamics in a growin hyphae of the fungus aspergillus nidulans (Chevallier et al).    C. Numerical simulation of a yeast spore and its cell wall (colors) and poalrity domain (white). D. Simulation of growth speed f yeast cells.

 

Funding:: ANR; Fondation de la Recherche Médicale ; FungiBrain (European ITN) FP7.

Collaborations: Arezki Boudaoud (Ecole Polytechnique); Etienne Couturier (MsC, Paris); Yolanda Sanchez (U. Cordoba); Miguel Peñalva (U. Madrid).

Keywords: Polarirty, Cell wall, Mecanbiology, Cytoskeleton, Fungi and yeast.

 

Video2

Legend: Growth and division of yeast cells expressing fluorescent markers of the nuclear envelop and cell wall synthesis.