Nédélec Group
Cellular architecture
An array of mitotic spindles obtained in vitro with Xenopus laevis egg extracts.
Previous and current research
Modern microscopy has demonstrated the dynamic nature of biological organisation. The mitotic spindle, for example, is a stable and solid cellular structure; in a given cell type, it has a precise symmetry and very reproducible dimensions. Yet, while the chromosomes are stable, all the other components of a spindle – polar filaments called microtubules and associated proteins - are in rapid turnover. Microtubules grow, shrink and disappear in a matter of minutes and proteins continuously and stochastically bind and unbind. The resulting assembly is highly dynamic and yet stable and remarkably precise; it can remain steady for hours, until it eventually applies the balanced forces necessary to position and segregate the chromosomes exactly.
The spindle is thus a fascinating structure, which illustrates a central question in biology: how can the uncoordinated and inevitably imperfect actions of proteins and other molecules collectively fulfill the biological needs with the required accuracy?
Today, understanding biological phenomena from their multiple biological components - systems biology - is a cutting-edge research topic. The collective behaviour in biology is more than a simple statistical average. It is a challenging problem for many reasons: 1) the diversity of molecular players is enormous; 2) their interactions are oft en dynamic and out-of-equilibrium; 3) the properties of the constituents have been selected by natural evolution.
We approach this topic in practical terms by developing in vitro experiments and modelling tools. The in vitro approach allows us to reduce the number of components in the system: we can either remove specific proteins, or start from scratch by mixing purified components. Modelling allows us to recapitulate the process of protein organisation in a framework in which all the interactions are known exactly and can even be specified at will. In the past, we developed innovative numerical methods to simulate the collective behaviour of multiple polar fibres and of their associated proteins. They are implemented in a simulation engine called cytosim, which is also made available to our community. Simulations are oft en used to validate or refute existing ideas, but we also try to use them in a more creative way: one can generate systematically various properties for the molecules, and automatically test their ability to form stable structures. The analysis of successful scenarios leads to the formulation of new hypotheses.
Future projects and goals
We will study systems in which experiments and theory can be synergistically combined. We currently focus on Xenopus egg extracts, an experimental system in which many aspects of mitosis can be recapitulated. We are also generally interested in modelling cellular processes in which the cytoskeleton is a major player, such as the different stages of mitosis, the generation of cell shape in S. pombe, or the generation of asymmetry during cell division.