Vladana Vukojevic, Karolinska Institute: Quenching Small-Amplitude Limit Cycle Oscillations for Predictive Modeling of Complex Molecular Mechanisms Underlying Chemical and Biochemical Oscillatory Reactions. Insights into the Effects of Ethanol on the Hypo

Vukojevic_20241014
10/17/2024
 | 
3 PM (US Eastern)
https://iu.zoom.us/meeting/register/tZYqd-2srD8tGtCXDem4Cka08rBz5fDW0EQR

Quenching Small-Amplitude Limit Cycle Oscillations, i.e., Quenching Analysis (QA), is a method specifically designed to take the advantage of the oscillatory dynamics that emerges in the vicinity of a supercritical Hopf bifurcation and harvest it to acquire unique quantitative information about the investigated system that can easily be compared with model predictions. To this aim, QA relies on a series of controlled additions of a compound that is inherent to the system or reacts with a reactive species in the system, to immediately, yet temporarily suppress the oscillations. For each species, QA yields two values, the quenching concentration (qi), i.e., the amount of species i needed, and the quenching phase (ji), i.e., the phase angle with respect to a reference point in an oscillation, at which this amount is to be added to temporarily pause the oscillations. By comparing the experimentally derived quenching concentrations and quenching phases with results obtained from mechanistic models, one can determine whether key reaction pathways are correctly identified and incorporated in the model of the reaction mechanism and assess how realistically the model reflects the true mechanism of the investigated system. The aim of this presentation is twofold: to present the theoretical background behind QA and to demonstrate the potential of this method for understanding specific features of a complex neuroendocrine dynamical system, the Hypothalamic-Pituitary-Adrenal (HPA) axis, under normal physiology and response to ethanol-induced stress.

  1. Čupić Ž, Stanojević A, Marković VM, Kolar-Anić L, Terenius L, Vukojević V. The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations. Addict. Biol. 2017 22(6):1486-1500. doi: 10.1111/adb.12409
  2. Abulseoud OA, Ho MC, Choi D-S, Stanojević A, Čupić Ž, Kolar-Anić Lj, Vukojević V. Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat experimental observations and mathematical modelling. PLoS One 2017, 12(5):e0177551. doi: 10.1371/journal.pone.0177551
  3. Stanojević A, Marković VM, Čupić Ž, Kolar-Anić Lj, Vukojević V. Advances in mathematical modelling of the hypothalamic–pituitary–adrenal (HPA) axis dynamics and the neuroendocrine response to stress. Current Opinion in Chemical Engineering 2018, 21:84–95. doi:10.1016/j.coche.2018.04.003

Vukojevic_20241014

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