Constraint-based modeling of metabolism - interpreting predictions of growth and ATP synthesis in human and yeast
Doctoral thesis, 2019
the Crabtree effect
the Warburg effect
flux balance analysis
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Predicting growth of the healthy infant using a genome scale metabolic model.
NPJ systems biology and applications,; Vol. 3(2017)p. 3-
Nilsson, A., Haanstra, J.R., Engqvist, M., Gerding, A., Bakker, B., Klingmüller, U., Teusink, B. and Nielsen, J. Liver cancer cells excrete glutamate of cytosolic but not mitochondrial origin
Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase
Scientific Reports,; Vol. 6(2016)
Nilsson, A., Björnson, E., Flockhart, M., Larsen, F., Nielsen, J. Complex I is bypassed during high intensity exercise
Metabolic Models of Protein Allocation Call for the Kinetome
Cell Systems,; Vol. 5(2017)p. 538-541
Introductory text in journal
I used constraint based models of metabolism to study growth and production of ATP. Several findings came out of the simulations. 1) Breastfed infant’s growth is constrained by the rate of ATP production. 2) Cells can switch enzymes to increase the rate of ATP production. But this comes at the cost of a more wasteful extraction of nutrients. The behavior of both yeast cells, cancer cells and human muscles can be explained by this. 3) The rate of growth can be predicted for cells that are fed different nutrients. 4) Cancer cells excrete glutamate because it is a byproduct of growth. The rate of growth in cancer cells can be decreased by blocking glutamate excretion.
Computer models are powerful tools. They allow knowledge to be integrated from different scientific studies and experiments. The models make predictions about reality. By interpreting the predictions it is possible to extract knowledge that may have been overlooked. Computer models highlight gaps in human knowledge. They advance our understanding of cells towards future improvements of human health.
Integrating Modelling of Metabolism and Signalling towards an Application in Liver Cancer (ERASysAPP - IMOMESIC)
Swedish Research Council (VR), 2014-10-01 -- 2018-09-30.
Biochemistry and Molecular Biology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Bioinformatics and Systems Biology
Areas of Advance
Life Science Engineering (2010-2018)
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4534
Chalmers University of Technology
KC-salen, Kemihuset, Kemigården 4, Göteborg
Opponent: associate professor Tomer Shlomi, Department of Computer Science and Biology, Technion - Israel Institute of Technology, Israel.