Developing a stochastic model of folate-mediated one-carbon metabolism
Develop an accurate mathematical representation of the folate-mediated one-carbon metabolism (FOCM) as an interconnected network of metabolic pathways, including those required for the de novo synthesis of dTMP and purine nucleotides and for remethylation of homocysteine to methionine.
What we did
We developed a hybrid computational model comprised of ordinary differential equations and stochastic simulation. We investigated whether the de novo dTMP synthesis pathway was sensitive to perturbations in FOCM that are known to be associated with human neural tube defects (NTDs).
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Misselbeck K, Marchetti L, Field MS, Scotti M, Priami C, Stover PJ, A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis. Sci Rep 7, 797, 2017. See 0.1038/s41598-017-00854-w
Misselbeck K, Marchetti L, Priami C, Stover PJ, Field MS, The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism, Sci Rep 9, 4322, 2019. See 10.1038/s41598-019-40230-4