Email : jacques [dot] pecreaux [at] univ-rennes1 [dot] fr
Phone : +33 (0)2 23 23 45 03
My research aims to understand the origin of the extraordinary faithfulness of cell division - an ambivalent property, allowing the development of multicellular organisms but also pathology such as cancer. In an original approach, I am interested in the mechanical origins of this robustness, id est the role of the dynamics of the components, the forces they generate, their displacement, and the feedback loops modulating these properties with cell environment. To do this, we use extensive image and data processing and numerical simulations to quantitatively establish the physical models expressed in the form of equations. This interest in interdisciplinary approaches, combining fundamental research, (reverse) engineering and methodological developments, finds its origin in my course. After an engineering degree from École Polytechnique (Palaiseau), I continued with a DEA (~master) in physics of liquids (Paris VI) and a PhD (1999-2004, supervisor Patricia Bassereau, Physico-Chimie Curie, Paris) on a model system for biology, the giant lipid vesicles. I have already implemented an interdisciplinary approach to understand the role of cell membrane undulations. Fascinated by the living, I pursued such approaches on cell division, using the nematode, a classic model organism, in the laboratories of Joe Howard and Tony Hyman (Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany). After obtaining the ATIP-Avenir starting grant in 2011, I created the "Reverse Engineering Cell Division" lab. I was recruited by the CNRS as CR1 the following year. Beyond the division's fundamental understanding, we develop the necessary mathematical and computational methods up to patenting microscopy techniques and creating a start-up (Inscoper).
Recently, I have been interested in three lines of research together with my lab:
Firstly, we investigated the positioning of the mitotic spindle. We suggested that despite the large size of the zygote of the nematode C. elegans, the mitotic spindle is held in the centre during metaphase is achieved by astral microtubules pushing against the periphery of the cell. Besides, the stability is increased by the buckling of the microtubules, id est, their bending under the pushing exerted on the extremities (Pecreaux et al., 2016).
We also explored the regulation of pulling forces from the cortex that position the spindle. This regulation is threefold, as revealed by a detailed analysis of microtubules' dynamics in the cortex (Bouvrais et al., 2021). Three independent controls carry out this triple regulation:
- The progression of mitosis via the persistence of dynein molecular motors to pull on the astral microtubules;
- The position of the centrosomes, as we have recently demonstrated, conferring robustness on the final positioning of the spindle (Bouvrais et al., 2018);
- The polarity, which results in a greater attachment rate of dynein motors to astral microtubules on the posterior side (Rodriguez-Garcia et al., 2018)
Using signal analysis methods, we also studied the mitotic spindle's mechanical behaviour, seen as a structure connecting the two poles. We observed that its length is not maintained in metaphase but instead undergoes a slow evolution. It also suggests the adaptability of the spindle (Mercat, 2016). Interestingly, the principal component analysis of spindle elongation under different conditions (RNAi and mutants) points in the same direction. It also suggests that only three independent moduli govern spindle elongation.
Finally, wishing to validate these results in cultured cells without resorting to chemical synchronization, we have innovated to create a new microscope together with Marc Tramier's team. It is more efficient in its management to capture brief events such as contacts of microtubules or dynein to the cortex (Bouvrais et al., 2021; Rodriguez-Garcia et al., 2018; Sizaire et al., 2020). We patented this approach and promoted it by creating the inscoper startup, of which I am a scientific advisor (Roul et al., 2015). We now wish to enslave microscope driving by grabbed images. It requires classifying images to make the microscope "intelligent" and have patented this development (Balluet et al., 2020).
With my lab, we are now focusing on "the robustness and adapting mechanics of cell division". It is because cell division is very faithful when it comes to distributing chromosomes to daughter cells correctly. This ability to function robustly despite internal defects (for example, aberrant chromosome numbers as in cancer cells) or external ones (changes in shape or environment) remains enigmatic. This robustness beyond its ambivalence also questions Boveri's hypothesis that whether a defect in chromosome partitioning causes cancer is neutral or favouring resistance. It calls for further research. Furthermore, checkpoints' mere existence is not sufficient to prevent defects as exemplified by merotelic attachment defects, which can trick the checkpoint and cause chromosomal aberrations. I hypothesize that the mechanics of the spindle and, more broadly, of the surrounding cell are involved. Finally, we ask ourselves to what extent these properties are general to all cells. To test our results on cultured cells, we continue to develop the roboscope, our stand-alone microscope together with Marc Tramiers's lab and Inscoper, SAS as well as Photonlines, SAS.
Bouvrais, H., Chesneau, L., Cunff, Y.L., Fairbrass, D., Soler, N., Pastezeur, S., Pécot, T., Kervrann, C., and Pécréaux, J. (2021). The coordination of spindle-positioning forces during the asymmetric division of the C. elegans zygote is revealed by distinct microtubule dynamics at the cortex. EMBO reports, (accepted).
Bouvrais, H., Chesneau, L., Pastezeur, S., Fairbrass, D., Delattre, M., and Pecreaux, J. (2018). Microtubule Feedback and LET-99-Dependent Control of Pulling Forces Ensure Robust Spindle Position. Biophys J 115, 2189-2205.
Mercat, B. (2016). Analyse temps-fréquence en mécanique cellulaire et adaptabilité du fuseau mitotique. (supervisé par Hélène Bouvrais et Jacques Pécréaux). https://ecm.univ-rennes1.fr/nuxeo/site/esupversions/1c891a90-861d-4436-8224-c5e396510934
Pecreaux, J., Redemann, S., Alayan, Z., Mercat, B., Pastezeur, S., Garzon-Coral, C., Hyman, A.A., and Howard, J. (2016). The mitotic spindle in the one-cell C. elegans embryo is positioned with high precision and stability. Biophys J 111, 1773-1784.
Rodriguez-Garcia, R., Chesneau, L., Pastezeur, S., Roul, J., Tramier, M., and Pecreaux, J. (2018). The polarity-induced force imbalance in Caenorhabditis elegans embryos is caused by asymmetric binding rates of dynein to the cortex. Mol Biol Cell, mbcE17110653.
Balluet, M., Pont, J., Giroux, B., Bouchareb, O., Chanteux, O., Tramier, M., and Pécréaux, J. (2020). Method for managing command blocks for a microscopy imaging system, corresponding computer program, storage means and device, Patent pending.
Roul, J., Pecreaux, J., and Tramier, M. (2015). Method for controlling a plurality of functional modules including a multi-wavelength imaging device, and corresponding control system, Patent FR, US, (pending in EU).
Sizaire, F., Le Marchand, G., Pecreaux, J., Bouchareb, O., and Tramier, M. (2020). Automated screening of AURKA activity based on a genetically encoded FRET biosensor using fluorescence lifetime imaging microscopy. Methods Appl Fluoresc 8, 024006.