Modeling the molecular regulatory mechanism of the Neurospora circadian clock.
with Albert Goldbeter (ULB)
We proposed and analysed mathematical models based on the negative autoregulation of the frq gene that underlies the Neurospora circadian rhythm. The model accounts for the occurrence of these oscillations in constant environmental conditions (e.g. constant darkness), for entrainment of these rhythms by light-dark cycles, for their phase-shifting induced by light pulses and for temperature compensation.

Study of the robustness of circadian rhythms to molecular noise.
with José Halloy and Albert Goldbeter (ULB)
Intrinsic molecular fluctuations may result from the small numbers of protein and mRNA molecules involved in the oscillations at the cellular level. In these conditions, it becomes necessary to resort to stochastic simulations to assess the influence of molecular noise on circadian oscillations. We addressed the effect of molecular noise by considering the stochastic version of the deterministic models and by applying specific algorithms to simulate these stochastic models.

Coupling and synchronization of circadian oscillators.
with Samuel Bernard, Hanspeter Herzel, and Achim Kramer (HU Berlin)
and with Marc Hafner (EPFL Lausanne)
The suprachiasmatic nuclei (SCN) of the hypothalamus is known as the center of the circadian clock. It contains the pacemaker which controls peripheral clocks present in other parts of the brain as well as in peripheral tissues. The SCN structure is highly heterogeneous. A fundamental issue with regard to the organization of the circadian system is how the SCN achieve a coherent output while the individual cellular oscillators express a wide range of phases and periods and how this system integrates light signals. In order of getting more understanding of this organisation, we study the dynamic properties of coupled circadian oscillators. (See movie)

Assessing the relationship between protein complexes and gene expression in yeast.
with Nicolas Simonis, Shoshana Wodak, and Jacques van Helden (BiGRe lab, ULB)
Since interacting proteins must be simultaneously present in a cell, they should be synthetized together in (at least) some conditions. Based on this expectation, we applied two approaches to evaluate the relationship between protein complexes and gene expression data. In the first one, we compare complexes with clusters of co-regulated genes, while the second one, we quantify the correlation of expression profiles of genes involved in the same complex

Genome-scale regulatory sequences analysis in yeast
with Jacques van Helden (BiGRe lab, ULB)
We have applied bioinformatics analysis in order to uncover the regulatory binding sites in genes involved in phosphate and sulfured amino acid (methionine and cysteine) metabolisms in Saccharomyces cerevisiae and to predict the transcriptional response at the genome level in yeast.