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Systems biology of the AMP-activated protein kinase pathway


Biology is moving from describing phenomena to understanding design principles and dynamic operation of cellular modules, entire cells, and even organisms. The quantitative approach to biological systems is driven by technological advances and close collaboration between different disciplines. Understanding properties of biological systems holds significant promises for drug development, treatment of diseases or improving bioprocesses. In this project, experimental and theoretical studies will be integrated to achieve a better understanding of the dynamic operation of the AMP-activated protein kinase (AMPK) signalling pathway. This pathway plays a central role in monitoring the cellular energy status and trolling energy production and sumption. The ceptional project idea is to generate kinetic mathematical descriptions of pathway activation/deactivation in yeast and mammalian cells. The approach will be highly systematic. A first network model will be generated based on existing data. A standard dataset, including diverse data such as relative and absolute protein, mRNA and metabolite levels and capturing the dynamics of the pathway, will be used to establish kinetic models of yeast and mammalian AMPK. These models will be improved and optimised iteratively in several rounds. A major challenge will be the attempt to use information from the yeast model to fill gaps in the model describing mammalian AMPK. The computational models will support drug development at an SME that is fully integrated into all project activities, If successful, the results will have major payoff to tackle some of the most rapidly advancing diseases in the modern world, obesity and type-2 diabetes. Hence, the project will result in a case study for employing systems biology in drug target identification and in drug development and it will produce results exploitable also for engineering of microbial metabolism and systems biology software development.

Call for proposal

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100 Göteborg

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Participants (5)