Nédélec Group

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 its main components – polar filaments called microtubules – are in rapid turnover. They grow, shrink and disappear in a matter of minutes, within a spindle that may remain steady for hours. Chromosomes and microtubules are connected by proteins which continuously and stochastically bind and unbind. The resulting assembly is highly dynamic and yet stable and remarkably precise; it 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 molecules result in a structure able to fulfill its biological function with the utmost accuracy?

Obviously, understanding the collective behaviour is the challenge here, but it cannot be deduced from a simple statistical average. It is a challenging problem for several reasons: 1) the diversity of molecular players is often enormous; 2) their interactions are often dynamic and out-of-equilibrium; and 3) the properties of the proteins have been selected for the biological task by natural evolution. Understanding biological phenomena from their multiple biological components – systems biology – is a cutting-edge research topic.

We address this problem 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 a specific protein, 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 often used to validate or refute existing ideas, but we 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 inmodeling 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.