Browsing by Author "Demir, Guleser Kalayci"

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Citation - WoS: 1
Citation - Scopus: 1
Coupling of cell fate selection model enhances DNA damage response and may underlie BE phenomenon
(INST ENGINEERING TECHNOLOGY-IET, 2020) Goekhan Demirkiran; Guleser Kalayc Demir; Cuneyt Guzelis; Guzelis, Cuneyt; Demirkiran, Goekhan; Demir, Guleser Kalayci
Double-strand break-induced (DSB) cells send signal that induces DSBs in neighbour cells resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three-mode two-dimensional oscillators which models the p53-mediated cell fate selection in globally coupled DSB-induced cells. The coupled model consists of ATM and Wip1 proteins as variables. The coupling mechanism is realised through ATM variable via a mean-field modelling the bystander signal in the intercellular medium. Investigation of the model reveals that the coupling generates more sensitive DNA damage response by affecting cell fate selection. Additionally the authors search for the cause-effect relationship between coupled p53 network oscillators and bystander effect (BE) endpoints. For this they search for the possible values of uncertain parameters that may replicate BE experiments' results. At certain parametric regions there is a correlation between the outcomes of cell fate and endpoints of BE suggesting that the intercellular coupling of p53 network may manifest itself as the form of observed BEs.
Citation - WoS: 5
Citation - Scopus: 5
Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model
(Institution of Engineering and Technology journals@theiet.org, 2018) Gökhan Demirkıran; Güleser Kalayci Demir; Cüneyt Güzeliş; Guzelis, Cuneyt; Demirkiran, Gokhan; Demir, Guleser Kalayci
This study proposes a two-dimensional (2D) oscillator model of p53 network which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables and studies the impact of p53-regulators on cell fate decision. First the authors identify a 6D core oscillator module then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. This oscillator provides a mechanism that leads diverse modes underpinning cell fate each corresponding to a cell state. To investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on the characteristics of oscillations they introduce also a delay differential equation version of the 2D oscillator. They observe that the suppression of p53 inhibitors decreases the amplitudes of p53 oscillation though the suppression increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible targets for cancer therapies considering their impact on the oscillator supported by biological findings. They model some mutations as critical changes of the phase space characteristics. Possible cancer therapeutic strategies are then proposed for preventing these mutations' effects using the phase space approach. © 2018 Elsevier B.V. All rights reserved.