For marine photoautotrophs, light is a key environmental signal controlling a range of physiological and adaptive processes. In this talk, I will present two projects in our lab that focus on the role of light and photosynthesis on the physiology of marine phytoplankton. In the coastal diatom, Thalassiosira pseudonana, we have identified a protein that mediates photosynthetic responses under iron (Fe) limitation and high light. TpDSP1 is a Ca2+-binding, plastid-localized protein that, when over-expressed in T. pseudonana, significantly increases fitness under Fe limitation by increasing growth rates, photosynthetic efficiency, and cyclic electron flow around photosystem I. However, TpDSP1 also conferred a physiological disadvantage whereby over-expression led to increased sensitivity to high light, forcing cells to walk an ecological ‘tightrope’ through the regulation of this protein. In the second part of my talk, I will discuss the role of light in mediating host-virus interactions. Microalgal viruses are inherently dependent on light and host…

Growth is a highly optimized process in bacteria since the battle for the conquest of ecological niches is though. Understanding the key elements governing the growth rate management is then crucial to further understand and predict the bacterium behavior with respect to various environmental conditions. In this context, we have proposed in [Goelzer et al, Automatica 2011], a promising theoretical framework, so-called Resource Balance Analysis (RBA) formalizing the problem of resource repartition at the cell scale as a convex optimization problem. In this talk, we present the biological validation of this theoretical framework by applying it on the Gram-positive model bacterium Bacillus subtilis. To this end, through the European Project BasynTech, we have generated a dedicated and large fluxomic and proteomic datasets for grown in various conditions. We have used these data to calibrate/validate our RBA method leading to successful identification of over 600 parameters, including estimated activities of individual enzymes under…

In the last decade there has been an increasing amount of experimental and computational evidence pointing out that the proteome of eukaryotes and viruses is enriched in intrinsically disordered protein (IDPs) and/or intrinsically disordered regions (IDRs). IDPs/IDRs are ubiquitous functional proteins that lack stable II and III structures under physiological conditions in the absence of a partner and that rather exist as highly dynamic conformational ensembles. IDPs are often involved in biological processes implying manifold protein-protein interactions, such as cellular regulation, transcription and signal transduction.In the course of the structural and functional characterization of the measles virus replicative complex, we discovered that the nucleoprotein (N) and the phosphoprotein (P) contain long (up to 230 residues) disordered regions possessing sequence and biochemical features that typify IDPs. More recently, by combining computational and experimental approaches, we extended these results to the N and P proteins from the newly emerged Nipah and Hendra viruses. My…

Combining genomic analyses with evolution experiments provides a dynamic view of virtually all cellular processes. Indeed, the full revivable fossil record produced in such experiments can be investigated for phenotypic, genomic and global expression changes. During the longest-running evolution experiment with Escherichia coli, adaptive changes have been shown to strongly affect the sequence, structure and expression of evolved genomes, with sometimes unexpected phenotypic outcomes.

Genome architecture (size, proportion of coding sequences, polycistronic mRNAsŠ) is the consequence of many interacting forces acting over very long time scales. Indeed, selection, mutation biases, drift etc. all act directly or indirectly on the different genome compartments, either triggering their increase or decrease in size or proportion depending on the life style of the organisms (e.g., environment complexity, environment variation, population sizeŠ). Understanding how the intertwining of these pressures leads to particular architecture is difficult for at least three reasons. First, it is not clear how a given change of life-style will affect these different pressures.Second, it is impossible to experimentally separate these forces to observe their individual action since they are all interacting one with the others at the molecular level.Third, they act on time scales that are almost impossible to access experimentally, even with species reproducing rapidly. We propose that in silico experimental evolution approaches, in which simulated species…

Progress in medicine and biology has been so steep that data interpretation has now become an even greater bottleneck than data generation.These data are either structured or unstructured, i.e. found either in databases or in texts; and they tell about biological interactions within species or about evolutionary relationships among them.Our hypothesis is that it is possible to integrate all of these heterogeneous and massive data types coherently via a single network, and that in turn, the topological properties of this networks predict novel relationships and mechanisms that either explain the behavior of an organism as well as novel targets for drugs that modify it.Support for this hypothesis comes from multiple predictions that are experimentally validated, including:a) the identification of protein function and substrates with and without structures; andb) the elucidation of new post-translational modifier-protein target and Protein-Protein  Interaction pairs.Together with other evolutionary tools to identify disease-causing mutations and genes, this integrative network…

24-hour biological clocks are nearly ubiquitous amongst eukaryotes, controlling processes from the human sleep-wake cycle to flowering in plants. Linking the clock’s molecular mechanisms to high-level biological functions, timed to appropriate phases of the day/night cycle and the annual cycle of seasons, exemplifies the challenges of multi-scale systems biology. These “circadian” rhythms share similar properties across all organisms, even in some prokaryotes, yet the key ‘clock proteins’, rhythmic transcriptional regulators, are not conserved across taxa. We are testing the clock circuit in the plant Arabidopsis thaliana, combining molecular and reporter gene timeseries data, with clock mutants and environmental perturbations. The resulting mathematical models of the clock and its output pathways (Biomodels 55, 89, 214, 273, 295, 350, 412, 445) have predicted both particular molecular regulation and operating principles, such as the regulatory flexibility provided by interlocking, negative feedback loops. Testing these hypotheses in the tiny alga Ostreococcus tauri revealed a different strategy to gain flexibility in…