S E M I N A R I O del Área de Biofísica y Ciencia de Materiales.

Dr. José Díaz

Fac. de Ciencias-UAEM

 

Cells are dynamical systems characterized by a high degree of complexity due to an intricate network of subcellular processes that sustain their correct performance. This network is formed by a series of subnetworks with modular functioning, and among them is the subnetwork of biochemical processes that produces cell death or apoptosis.  In this work we deal with the dynamical behavior of the apoptotic pathway activated by ioniziting radiation (IR) like UV, gamma and X rays.

The stability of the steady state points, together with the nature of the bifurcation points, sets up the dynamical properties of a nonlinear system. In particular, nonlinear biochemical systems are characterized by a series of dynamical features like the existence of switches, hysteresis, and limit cycles, among others. In the special case of the apoptotic process, mathematical modeling is required for understanding its nonlinear complex behavior. Although previous attempts to model apoptosis were often limited to small systems, or based on qualitative data only, recent models are based on experimental data that give support to the theoretical results.

In this form, mathematical models have shown that the interactions between the nuclear molecular components of the intrinsic apoptotic pathway drive the system into a persistent limit cycle in the respective phase space after the application of high doses of ionizing radiation. Experimental data confirm the existence of this limit cycle, showing that this dynamical feature of the system relies on the existence of a p53-Mdm2 negative feedback loop, which is induced by a switch-like activation of the ATM kinase. 

 

 At the cytoplasm, the molecular dynamics that leads to the activation of the caspases sets up a saddle point bifurcation in the caspase 3-Bax degradation rate diagram. In this region of bistability, the saddle point bifurcation can drive the system either to a stable point with a high concentration of caspase 3 (cell death) or to a stable point with a low concentration of caspase 3 (cell survival). Out of this region, the system dynamics is settled on by the existence of a single stable fix point, which determines cell surviving independently of the concentration of caspase 3, i.e., there exits a threshold mechanism that regulates apoptosis and it is based on bistability, ultrasensitivity and irreversibility.

S E M I N A R I O   del   Área de Biofísica y Ciencia de Materiales.(svaldez-arroba-fis.unam.mx)

www.fis.unam.mx/seminarios_BiofCienciaMateriales.php

Participante: Dr. José Diaz-Facultad de Ciencias-UAEM

Institución: ¡¡¡ASPECTOS DINÁMICOS DE LA APOPTOSIS!!!

Lugar: Auditorio ICF

Fecha y hora: Este evento terminó el Martes, 20 de Septiembre de 2011