Browsing by Author "Demir, Güleser Kalayci"

Now showing 1 - 2 of 2

Citation - WoS: 6
Citation - Scopus: 7
Discriminant-based bistability analysis of a TMG-induced lac operon model supported with boundedness and local stability results
(Tubitak Scientific & Technological Research Council Turkey, 2016) Levent Cavas; Neslihan Avcu; Hakan Alyuruk; Güleser Kalaycı Demir; Cüneyt GÜZELİŞ; Ferhan PEKERGİN; Pekergin, Ferhan; Demir, Güleser Kalayci; Guzelis, Cuneyt; Kalayci Demir, Guleser; Cavas, Levent; Avcu, Neslihan; Alyuruk, Hakan
This paper presents the results of a theoretical and numerical study on the analysis of bistable behavior of the most studied gene regulatory network the lac operon in terms of the model parameters. The boundedness of the state variables for the considered model are demonstrated the parameter values providing the existence of the multiple equilibria and thus the bistable behavior are determined and a local stability analysis of the equilibria is performed. The parameter region yielding the existence of multiple equilibria is determined in an algebraic way based on discriminants. The model given in the state equation form is defined by the ordinary differential equations with the rational right-hand sides constituted within Hill and Michaelis Menten approaches based on enzyme kinetics. The presented method can also be used in the parametric studies of other gene regulatory and metabolic networks given by state equations with rational right hand sides.
Citation - WoS: 5
Citation - Scopus: 6
Two-dimensional polynomial type canonical relaxation oscillator model for p53 dynamics
(Institution of Engineering and Technology journals@theiet.org, 2018) Gökhan Demirkıran; Güleser Kalayci Demir; Cüneyt Güzeliş; Güzelis, Cüneyt; Demirkiran, Gökhan; Demir, Güleser Kalayci
p53 network which is responsible for DNA damage response of cells exhibits three distinct qualitative behaviours, low state oscillation and high state which are associated with normal cell cycle progression cell cycle arrest and apoptosis respectively. The experimental studies demonstrate that these dynamics of p53 are due to the ATM and Wip1 interaction. This paper proposes a simple two-dimensional canonical relaxation oscillator model based on the identified topological structure of ATM and Wip1 interaction underlying these qualitative behaviours of p53 network. The model includes only polynomial terms that have the interpretability of known ATM and Wip1 interaction. The introduced model is useful for understanding relaxation oscillations in gene regulatory networks. Through mathematical analysis we investigate the roles of ATM and Wip1 in forming of these three essential behaviours and show that ATM and Wip1 constitute the core mechanism of p53 dynamics. In agreement with biological findings we show that Wip1 degradation term is a highly sensitive parameter possibly related to mutations. By perturbing the corresponding parameters our model characterizes some mutations such as ATM deficiency and Wip1 overexpression. Finally we provide intervention strategies considering our observation that Wip1 seems to be an important target to conduct therapies for these mutations. © 2018 Elsevier B.V. All rights reserved.