A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes.

We present an experimental and computational pipeline for the generation of kinetic models of metabolism, and demonstrate its application to glycolysis in Saccharomyces cerevisiae. Starting from an approximate mathematical model, we employ a "cycle of knowledge" strategy, identifying the steps with most control over flux. Kinetic parameters of the individual isoenzymes within these steps are measured experimentally under a standardised set of conditions. Experimental strategies are applied to establish a set of in vivo concentrations for isoenzymes and metabolites. The data are integrated into a mathematical model that is used to predict a new set of metabolite concentrations and reevaluate the control properties of the system. This bottom-up modelling study reveals that control over the metabolic network most directly involved in yeast glycolysis is more widely distributed than previously thought.

Fibre optics sensors in tear electrolyte analysis: towards a novel point of care potassium sensor.

The diagnosis of ocular disease is increasingly important in optometric practice and there is a need for cost effective point of care assays to assist in that. Although tears are a potentially valuable source of diagnostic information difficulties associated with sample collection and limited sample size together with sample storage and transport have proved major limitations. Progressive developments in electronics and fibre optics together with innovation in sensing technology mean that the construction of inexpensive point of care fibre optic sensing devices is now possible. Tear electrolytes are an obvious family of target analytes, not least to complement the availability of devices that make the routine measurement of tear osmolarity possible in the clinic. In this paper we describe the design, fabrication and calibration of a fibre-optic based electrolyte sensor for the quantification of potassium in tears using the ex vivo contact lens as the sample source. The technology is generic and the same principles can be used in the development of calcium and magnesium sensors. An important objective of this sensor technology development is to provide information at the point of routine optometric examination, which would provide supportive evidence of tear abnormality.

Crossing the boundaries delivering trans-disciplinary science in a disciplinary world.

Major research initiatives are increasingly drawing on multiple disparate disciplines and systems biology is a key exemplar. Trans-disciplinary research occurs where individual disciplinary traditions combine to create new shared knowledge that cannot be said to fit within the domain of any single discipline. Generation of new understanding of biological systems at the cell, organ, or organism level clearly meets these criteria, and we therefore consider systems biology research a truly trans-disciplinary undertaking. Aside from the technological challenges of combining research outcomes of the contributing disciplines, directing and managing the overall research program also presents a significant challenge. In this chapter, we discuss the challenges of and enablers to working across the broad range of disciplines that contribute to systems biology research; we discuss potential management models that may be adopted and the features, benefits, and drawbacks of each, introducing examples of management models adopted at two UK Systems Biology Centres.

Uranyl-specific binding at a functionalised interface: a chemophotonic fibre optic sensor platform.

Detection of radiological materials in the solution phase is restricted by conventional radiation-counting techniques owing to extreme attenuation. Chemical sensing of the resultant radiological species such as uranyl UO(2)(2+) is possible on the surface of a plastic or glass fibre optic. A dihydroxy isoamethryin complex is tethered to the fibre surface which has a large extinction coefficient (119 000 M(-1) cm(-1) at lambda = 439 nm) and changes colour upon binding UO(2)(2+). The spectral changes are greater on the surface than in solution and binding is specific to UO(2)(2+) with small interferences from Gd(3+). Monitoring the spectral response in three detector bands in the red, green and blue enable the optical power change to be measured with sensitivities of 1 mdB, allowing UO(2)(2+) to be detected confidently at 50-100 ppb levels. Real-time kinetic analysis enables discrimination between the target species and possible interferents.