Information transmission through a nonlinear molecular signaling system: erbb as a case study

• Autores: Elisa Beltrán Sáez
• Directores de la Tesis: Tomás Alarcón Cor (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2019
• Idioma: español
• Tribunal Calificador de la Tesis: Marta Ibañes Miguez (presid.), Isabel Serra Mochales (secret.), Saúl Ares García (voc.)
• Programa de doctorado: Programa de Doctorado en Matemáticas por la Universidad Autónoma de Barcelona
• Enlaces
  • Tesis en acceso abierto en: TESEO
• Resumen

  • The ability of organisms to extract and store information from their surroundings marked a revolution in the history of life. Cells, from prokaryots to eukaryots, use specific receptors inserted in their membranes to detect extracellular molecules that cannot cross into the cell, where cell decisions are taken. Hence, those membrane receptors represent an information channel through which the environmental information can affect cell behavior and adaptation. In this Thesis, we modeled information transmission through the ErbB system, a family of receptors involved in many different cellular behaviors, such as cell proliferation or migration. Therefore, dysregulation of ErbB receptors is at the core of what can be called \textit{information diseases}, that is, diseases that arise from the loss of the capacity to obtain and interpret extracellular information, i.e. tumor formation. Our results show a decrease in the information transmitted through the ErbB channel as the amount of ErbB receptors at the membrane increases. We considered different dynamics of the receptors and showed that the loss of information depends on the dynamics of interaction between the receptors, as well as on their interactions with the intracellular signaling machinery. In particular, we studied the interaction of active receptors with several signaling intracellular proteins and showed that the observed tendency of proteins to bind several binding sites with similar affinities translates into an increased synergy between the signaling proteins. All in all, quantifying and analysing these dependencies results in a better understanding of the dynamics and information transmission through ErbB and similar molecular systems.