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Modelling in biology becomes necessary when systems are complex but the more complex the systems are the harder the models become to read. The most common ways of writing models are by writing reactions on discrete, typed objects (e.g. molecules of different species), or writing rate equations for the populations of such species. One problem (1) with those approaches is that the number of species and reactions is often so large that the model cannot be realistically enumerated. Another problem (2) is that the number of species and reactions is fixed, whereas biology often grows new compartments which means new reactions and species. Here we develop an extension to the representation of reactions where the objects carry variables that are defined by their type (for example objects of type Leaf all have a Mass variable). The dynamics are defined by rules about types, which means they work for all objects of that type. This compact representation solves problem 1. If we think of the object variables as the analogue of reaction/rate equation species, creating a new object of some type means we are also creating new species (solving problem 2). We also developed an embedding of Chromar in the programming language Haskell and showed its applicability to two examples. Having a more compact representation can help make models a tool for knowledge representation and exchange instead of just a simulation input. Embedding Chromar in a general purpose programming language lifts some of the constraints of modelling languages while still maintaining the naturalness of a domain-specific language.

Ostreococcus tauri is a unicellular green alga and amongst the smallest and simplest free-living eukaryotes. The O. tauri genome sequence was determined in 2006. Molecular, physiological and taxonomic data that has been generated since then highlight its potential as a simple model species for algae and plants. However, its proteome remains largely unexplored. This paper describes the global proteomic study of O. tauri, using mass spectrometry-based approaches: phosphopeptide enrichment, cellular fractionation, label-free quantification and 15N metabolic labeling. The O. tauri proteome was analyzed under the following conditions: sampling at different times during the circadian cycle, after 24 h of illumination, after 24 h of darkness and under various nitrogen source supply levels. Cell cycle related proteins such as dynamin and kinesin were significantly up-regulated during the daylight-to-darkness transition. This is reflected by their higher intensity at ZT13 and this transition phase coincides with the end of mitosis. Proteins involved in several metabolic mechanisms were found to be up-regulated under low nitrogen conditions, including carbon storage pathways, glycolysis, phosphate transport, and the synthesis of inorganic polyphosphates. Ostreococcus tauri responds to low nitrogen conditions by reducing its nitrogen assimilation machinery which suggests an atypical adaptation mechanism for coping with a nutrient-limited environment.

The E3 ubiquitin ligase COP1 (CONSTITUTIVE PHOTOMORPHOGENIC1) plays a key role in the repression of the plant photomorphogenic development in darkness. In the presence of light, COP1 is inactivated by a mechanism which is not completely understood. This leads to accumulation of COP1’s target transcription factors, which initiates photomorphogenesis, resulting in dramatic changes of the seedling’s physiology.Here we use a mathematical model to explore the possible mechanism of COP1 modulation upon dark/light transition in Arabidopsis thaliana based upon data for two COP1 target proteins: HY5 and HFR1, which play critical roles in photomorphogenesis. The main reactions in our model are the inactivation of COP1 by a proposed photoreceptor-related inhibitor I and interactions between COP1 and a CUL4 (CULLIN4)-based ligase. For building and verification of the model, we used the available published and our new data on the kinetics of HY5 and HFR1 together with the data on COP1 abundance. HY5 has been shown to accumulate at a slower rate than HFR1. To describe the observed differences in the timecourses of the “slow” target HY5 and the “fast” target HFR1, we hypothesize a switch between the activities of COP1 and CUL4 ligases upon dark/light transition, with COP1 being active mostly in darkness and CUL4 in light. The model predicts a bi-phasic kinetics of COP1 activity upon the exposure of plants to light, with its restoration after the initial decline and the following slow depletion of the total COP1 content. CUL4 activity is predicted to increase in the presence of light. We propose that the ubiquitin ligase switch is important for the complex regulation of multiple transcription factors during plants development. In addition, this provides a new mechanism for sensing the duration of light period, which is important for seasonal changes in plant development.

SummaryThe 24-hour rhythms of the circadian clock [1] allow an organism to anticipate daily environmental cycles, giving it a competitive advantage [2, 3]. Although clock components show little protein sequence homology across phyla, multiple feedback loops and light inputs are universal features of clock networks [4, 5]. Why have circadian systems evolved such a complex structure? All biological clocks entrain a set of regulatory genes to the environmental cycle, in order to correctly time the expression of many downstream processes. Thus the question becomes: What aspects of the environment, and of the desired downstream regulation, are demanding the observed complexity? To answer this, we have evolved gene regulatory networks in silico, selecting for networks that correctly predict particular phases of the day under light/dark cycles. Gradually increasing the realism of the environmental cycles, we have tested the networks for the minimal characteristics of clocks observed in nature: oscillation under constant conditions, entrainment to light signals, and the presence of multiple feedback loops and light inputs. Realistic circadian gene networks are found to require a nontrivial combination of conditions, with seasonal differences in photoperiod as a necessary but not sufficient component.

Metathesis of Tp P r MoO 2 Cl (Tp P r = hydrotris(3-isopropylpyrazolyl)borate) with phenol/NEt 3 or thiol/NEt 3 mixtures results in the formation of air-stable, diamagnetic cis-dioxo-Mo(VI) complexes, Tp P r MoO 2 X (X = OC 6 H 4 sBu-2, OC 6 H 4 R-3 (R = Me, t Bu), OC 6 H 4 R-4 (R = Br, Et, OMe), OC 6 H 3 'Bu 2 -3,5, OC 6 H 3 'BuMe-2,4, S n Bu, S s Bu). The complexes were characterized by analytical, spectroscopic and mass spectrometric methods, which support the formulations, ligands present [IR: v(MoO 2 ) approximately 930 and 900 cm - 1 , v (BH) 2570-2480 cm - 1 , OAr 1605-1500 and 1300-1250 cm - 1 ] and assigned molecular symmetries ( 1 H/ 1 3 C NMR). Electrochemical studies revealed reversible or quasi-reversible (X = OC 6 H 3 'BuMe-2,4), one-electron reduction processes with E 1 / 2 values linearly correlated with the electron donor capacity of the ligand X (as expressed by Hammett functions). Oxygen atom transfer and comproportionation resulted in the formation of [Tp*MoO(OPh)] 2 (μ-O) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) in the reaction of Tp*MoO 2 (OPh) with PEt 3 in toluene (in contrast to the formation of phosphine oxide complexes in the Tp P r system), while hydrolysis of Tp*MoOCl 2 produced [Tp*MoOCl] 2 (μ-O). Reaction of Tp P r MoO 2 Cl with P(O i Pr) 3 produced [Tp P r MoOCl](μ-O)[Tp P r MoO(OH)]. The X-ray crystal structures of [Tp*MoOCl] 2 (μ-O) and [Tp P r MoOCl](μ-O)[Tp P r MoO(OH)] are reported. Both compounds exhibit corner shared bioctahedral structures with a single bridging oxo ligand linking TpxMoOX (X = Cl, OH) moieties. Chlorine atom transfer from Tp P r MoOCl 2 to PPh 3 in pyridine (py) or lutidine (lut) produces Tp P r MoOCl(py) and Tp P r MoOCl(lut), respectively.

Conventional, forward genetics has identified several molecular components of circadian clocks. Many additional loci and genetic interactions have recently been implicated in rhythmic control by a major effort in mapping quantitative trait loci (QTL) in the mouse. Reconciling the QTL with previous results both from QTL and mutagenesis will be a challenge for rhythm researchers.

Light sensitivity and the involvement of unstable proteins are key features of circadian clocks. Both photoreception and ubiquitin conjugation may be associated with nuclear regulators encoded by genes recently identified in Arabidopsis.

A similar version of this paper was also published in the Association of Applied Biologists Conference on Integrated Agricultural Systems: Methodologies, Modelling and Measuring, Edinburgh, 2-4 June 2009 (eds. Macleod, M. et al.) Aspects of Applied Biology, 93, 2009 , p. 227 RONO: 00