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Una red de intercambio de fosforilación de proteínas diseñada con implicaciones para el descubrimiento de redes

Deepak Mishra^1,2,3, Tristan Bepler^3,4,5, Brian Teague⁶

¹Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Science (New York, N.Y.)

|July 2, 2021

Resumen

Los investigadores diseñaron un interruptor de cambio rápido y sintético en la levadura utilizando la fosforilación de proteínas. Este trabajo también identificó cinco nuevas redes biológicas biestable que ocurren naturalmente, avanzando la biología sintética y la ingeniería celular.

Área de la Ciencia:

Biología sintética
Biología molecular y celular
La bioquímica

Sus antecedentes:

Las reacciones rápidas y reversibles son la clave para diseñar nuevos comportamientos celulares.
Los sistemas de regulación existentes a menudo se basan en mecanismos más lentos.
Las redes biológicas sintéticas ofrecen potencial para el control celular rápido.

Objetivo del estudio:

Para diseñar un interruptor sintético bistable en Saccharomyces cerevisiae utilizando la fosforilación proteína-proteína.
Desarrollar un marco computacional para la identificación de redes bistables endógenas.
Validar experimentalmente las redes biestables endógenas recién descubiertas.

Principales métodos:

Construcción de un interruptor sintético que utiliza una topología de represión cruzada con 11 elementos de fosforilación proteína-proteína.
Desarrollo de un marco computacional para la búsqueda de vías de proteínas endógenas para redes bistables.
Verificación experimental de la bistabilidad de las redes endógenas identificadas.

Principales resultados:

Se creó con éxito un interruptor sintético ultrasensible en levadura que cambia de estado en segundos y mantiene la bistabilidad a largo plazo.
Se han identificado y verificado experimentalmente cinco redes biológicas endógenas no notificadas anteriormente que presentan bistabilidad.
Demostró la utilidad del marco computacional para descubrir redes biológicas funcionales.

Conclusiones:

Las redes sintéticas de proteínas pueden ser rápidamente diseñadas para una regulación celular sofisticada.
El marco computacional desarrollado ayuda en el descubrimiento de redes endógenas con funciones específicas.
Esta investigación allana el camino para el diseño de sistemas de detección y procesamiento rápidos en bioingeniería.

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