Browsing by Author "Demir, Guleser Kalayc"

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Citation - WoS: 1
Citation - Scopus: 1
A 2-dimensional model of polynomial type for oscillatory ATM-Wipl dynamics in p53 network
(Institute of Electrical and Electronics Engineers Inc., 2017) Gökhan Demirkıran; Güleser Kalayci Demir; Cüneyt Güzeliş; Guzelis, Cuneyt; Demirkiran, Gokhan; Demir, Guleser Kalayc
Under gamma irradiation p53 gene regulatory network is able to exhibit three different modes namely low state oscillations and high state. There are experimental studies demonstrating that oscillatory behaviour of p53 is due to the interaction between upstream mediator of p53 i.e. ATM and a negative feedback loop formed by Wipl with that upstream. By proposing a canonical model based on ordinary differential equations made up of polynomial type birth and death terms we show mathematically that the simple interaction between ATM and Wipl is indeed able to exhibit three different behaviours relevant to DNA damage response of p53 network. We further carry out bifurcation analysis on the model with the aim of investigating the mutations such as Wip1 overexpression and ATM deficiency. Based on the proposed canonical model we show that Wipl is an important target for curing these types of mutations. © 2023 Elsevier B.V. All rights reserved.
Citation - WoS: 1
Citation - Scopus: 1
A 2-dimensional reduced oscillator model with rational nonlinearities for p53 dynamics
(Institute of Electrical and Electronics Engineers Inc., 2017) Gökhan Demirkıran; Güleser Kalayci Demir; Cüneyt Güzeliş; Guzelis, Cuneyt; Demirkiran, Gokhan; Demir, Guleser Kalayc
p53 tumour suppressor network plays the key role in DNA damage response of the cell. We present a comprehensive 2-dimensional oscillator model for p53 network dynamics. The model is reduced from the known 17-dimensional two-phase model of p53 network which shows temporary oscillatory behaviour under DNA damage type of Double Strand Breaks. The introduced oscillator model shows the same qualitative dynamics of two-phase model of p53 network such as bistability and oscillations when the parameters are adjusted accordingly. With the help of the identified oscillator in p53 network we introduce a new oscillator perspective: p53 network has an oscillator in the centre which other systems in the cell manipulate this oscillator to contribute to cell fate. The introduction of such low dimensional oscillator model will make it possible to study p53 network and the effects of other biological systems in the context of oscillations. © 2023 Elsevier B.V. All rights reserved.