Extracellular Signal Regulated Kinase (ERK) is an enzyme which plays an important role in multiple cell signalling processes, by catalysing the phosphorylation of a variety of substrates. ERK itself is activated by dual phosphorylation, at two different sites, by a second enzyme called mitogen-activated protein kinase kinase (MEK). The MEK/ERK pathway is involved in processes such as cell division, cell differentiation, and cell death. Mutations in the MEK/ERK pathway are associated with a range of diseases, including cancer; therefore, understanding the mechanisms and kinetics involved in the MEK/ERK pathway is an important step towards its exploitation as a therapeutic target.
Lewis Marsh from the Byrne lab, together with colleagues from the Mathematical Institute and the University of York, have undertaken a mathematical analysis of a recently published systems biology model by Yeung et al. Their previous analysis of the model relied on assumptions that the Byrne lab mathematically interrogated and confirmed using computational algebra and geometry. Marsh and colleagues analysed the kinetics of the ERK dual phosphorylation model with both wild-type and pathologically-relevant MEK mutant datasets with topological data analysis. Building on the work of Yeung et al, this study showcases how algebraic, geometric, and topological analysis methods can not only inform and surpass dynamical and statistical analyses of such models, but also guide future experimental design and research directions.
You can read the full publication in the Bulletin of Mathematical Biology.