June 20, 2022

Cüneyt Güzelis (Yaşar University, İzmir, Turquie)

Gene Regulatory Network (GRN), made of interacting regulators like DNA, RNA, proteins and their complexes, controls the expression levels of mRNA and proteins. GRNs govern several cellular processes such as metabolism, signaling, cell-differentiation, division, cycle arrest in response to DNA damage, and apoptosis.

Understanding dynamics of GRNs by introducing accurate models, then applying efficient mathematical/computational methods for their analysis is useful in identifying the underlying mechanisms of normal and abnormal cell functioning and hence developing drugs against diseases including cancer.

Bistability and oscillations are two crucial nonlinear dynamical behaviors observed in diverse areas of biological systems, in particular, gene regulatory networks. As in many others including electrical systems, bistability and oscillation phenomena appear as consequences of specific patterns of interactions such as positive/negative feedback loops among the components of GRN and have a certain function on the control of gene expression to regulate cellular processes and adaptation to changing environment. Bistability in GRN is a biological switching mechanism accompanied with hysteresis. It appears in a wide variety of GRNs including the lac operon of Escherichia coli, responsible for controlling the lactose metabolism under glucose starvation. Bistable genetic switches with their hysteresis characteristics behave as ON/OFF controllers avoiding unnecessary transitions between induced and uninduced states of the associated operon. Moreover, the oscillations in GRN, like circadian rhythm and 2-phase dynamics of tumor suppressor p53 network, are essentially of relaxation type providing constant amplitude and period, possessing self-sustaining property and ability of synchronization to the environmental inputs and interlinked networks.

The talk will present a series of studies on bifurcation and local stability analysis of some primary examples of bistable switches and relaxation oscillators appearing in GRNs.