| 1. |
- Achcar, F., et al.
(författare)
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The Silicon Trypanosome: A Test Case of Iterative Model Extension in Systems Biology
- 2014
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Ingår i: Advances in Microbial Physiology. - : Elsevier. - 0065-2911. - 9780128001431 ; 64, s. 115-143
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The African trypanosome, Ttypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of glycolysis in the bloodstream form of the parasite has been constructed and updated several times. The Silicon Trypanosome is a project that brings together modellers and experimentalists to improve and extend this core model with new pathways and additional levels of regulation. These new extensions and analyses use computational methods that explicitly take different levels of uncertainty into account. During this project, numerous tools and techniques have been developed for this purpose, which can now be used for a wide range of different studies in systems biology.
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| 2. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Metabolite Depletion Affects Flux Profiling of Cell Lines
- 2018
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 1362-4326 .- 0968-0004. ; 43:6, s. 395-397
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.
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| 3. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:19, s. 10294-10304
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Tidskriftsartikel (refereegranskat)abstract
- Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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