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- Dominiczak, AF, et al.
(författare)
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Systems biology to battle vascular disease
- 2010
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 25:4, s. 1019-1022
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Frey, S, et al.
(författare)
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A mathematical analysis of nuclear intensity dynamics for Mig1-GFP under consideration of bleaching effects and background noise in Saccharomyces cerevisiae
- 2011
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Ingår i: MOLECULAR BIOSYSTEMS. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 7:1, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Fluorescence microscopy is an imaging technique that provides insights into signal transduction pathways through the generation of quantitative data, such as the spatiotemporal distribution of GFP-tagged proteins in signaling pathways. The data acquired are, however, usually a composition of both the GFP-tagged proteins of interest and of an autofluorescent background, which both undergo photobleaching during imaging. We here present a mathematical model based on ordinary differential equations that successfully describes the shuttling of intracellular Mig1-GFP under changing environmental conditions regarding glucose concentration. Our analysis separates the different bleaching rates of Mig1-GFP and background, and the background-to-Mig1-GFP ratio. By applying our model to experimental data, we can thus extract the Mig1-GFP signal from the overall acquired signal and investigate the influence of kinase and phosphatase on Mig1. We found a stronger regulation of Mig1 through its kinase than through its phosphatase when controlled by the glucose concentration, with a constant (de)phosphorylation rate independent of the glucose concentration. By replacing the term for decreasing excited Mig1-GFP concentration with a constant, we were able to reconstruct the dynamics of Mig1-GFP, as it would occur without bleaching and background noise. Our model effectively demonstrates how data, acquired with an optical microscope, can be processed and used for a systems biology analysis of signal transduction pathways.
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- Garcia-Salcedo, Raúl, et al.
(författare)
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Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps
- 2014
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Ingår i: Febs Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 281:7, s. 1901-1917
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Tidskriftsartikel (refereegranskat)abstract
- The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1.
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- van Leeuwen, IMM, et al.
(författare)
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Dynamic energy budget approaches for modelling organismal ageing
- 2010
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Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 365:1557, s. 3443-3454
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Tidskriftsartikel (refereegranskat)abstract
- Ageing is a complex multifactorial process involving a progressive physiological decline that, ultimately, leads to the death of an organism. It involves multiple changes in many components that play fundamental roles under healthy and pathological conditions. Simultaneously, every organism undergoes accumulative ‘wear and tear’ during its lifespan, which confounds the effects of the ageing process. The scenario is complicated even further by the presence of both age-dependent and age-independent competing causes of death. Various manipulations have been shown to interfere with the ageing process. Calorie restriction, for example, has been reported to increase the lifespan of a wide range of organisms, which suggests a strong relation between energy metabolism and ageing. Such a link is also supported within the main theories for ageing: the free radical hypothesis, for instance, links oxidative damage production directly to energy metabolism. The Dynamic Energy Budgets (DEB) theory, which characterizes the uptake and use of energy by living organisms, therefore constitutes a useful tool for gaining insight into the ageing process. Here we compare the existing DEB-based modelling approaches and, then, discuss how new biological evidence could be incorporated within a DEB framework.
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