Modelling of world oil market An assessment of factors both economic and political affecting world oil production and consumption for the purpose of econometric analysis of historical data & medium term projections

SIGLEAvailable from British Library Document Supply Centre- DSC:D35563/81 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Propagation and control of gene expression noise with non-linear translation kinetics

•Hyperbolic translation greatly attenuates the propagation of mRNA noise to protein level.•Robustness strategies depend qualitatively on the kinetic order of translation.•Gene expression is less noisy than metabolic reactions.•Natural and synthetic systems could exploit hyperbolic translation to increase robustness. Gene expression is a stochastic process involving small numbers of molecules. As a consequence, cells in a clonal population vary randomly and sometimes substantially from one another in the concentration of mRNA and protein species, a phenomenon known as gene expression noise. Previous theoretical models of gene expression noise assumed that translation is first-order (linear) in mRNA concentration, leading to unfiltered propagation of mRNA noise to the protein level. Here I consider the biological ramifications of relaxing this assumption. Specifically, I solve for the noise statistics of gene expression assuming that translation obeys hyperbolic, Michaelis–Menten kinetics with respect to mRNA concentration. I generalize previous stochastic gene expression models by allowing the kinetic order of translation, denoted here by a, to vary continuously from zero-order (a = 0), where ribosomes are fully saturated with mRNA, to first order (a = 1), where ribosomes are unsaturated and mRNA is limiting for translation. In general, hyperbolic translation acts as a high-amplitude filter of mRNA noise. This hyperbolic filtering greatly attenuates the propagation of transcriptional noise to the protein level and qualitatively changes the selective and synthetic targets of noise control. In principle, natural selection or synthetic biologists could exploit this feature to limit or amplify gene expression noise by tuning mRNA and ribosome levels to control the kinetic order of translation

Single-molecule investigations of the stringent response machinery in living bacterial cells

The RelA-mediated stringent response is at the heart of bacterial adaptation to starvation and stress, playing a major role in the bacterial cell cycle and virulence. RelA integrates several environmental cues and synthesizes the alarmone ppGpp, which globally reprograms transcription, translation, and replication. We have developed and implemented novel single-molecule tracking methodology to characterize the intracellular catalytic cycle of RelA. Our single-molecule experiments show that RelA is on the ribosome under nonstarved conditions and that the individual enzyme molecule stays off the ribosome for an extended period of time after activation. This suggests that the catalytically active part of the RelA cycle is performed off, rather than on, the ribosome, and that rebinding to the ribosome is not necessary to trigger each ppGpp synthesis event. Furthermore, we find fast activation of RelA in response to heat stress followed by RelA rapidly being reset to its inactive state, which makes the system sensitive to new environmental cues and hints at an underlying excitable response mechanism

Microorganisms maintain crowding homeostasis

Macromolecular crowding affects the mobility of biomolecules, protein folding and stability, and the association of macromolecules with each other. Local differences in crowding that arise as a result of subcellular components and supramolecular assemblies contribute to the structural organization of the cytoplasm. In this Opinion article we discuss how macromolecular crowding affects the physicochemistry of the cytoplasm and how this, in turn, affects microbial physiology. We propose that cells maintain the overall concentration of macromolecules within a narrow range and discuss possible mechanisms for achieving crowding homeostasis. In addition, we propose that the term 'homeocrowding' is used to describe the process by which cells maintain relatively constant levels of macromolecules