Bacteriophage-based synthetic biology

Abstract

The biology is complex and there is a sort of organisms that interacts worldwide. In that big system, there are the viruses, organisms that are not “alive” while they are out of the host organism. When viruses enter inside the host cell, immediately start to use their own molecular machinery in combination with the host one, in order to produce the molecules that are encoded in their genes. The first interactions between the host (inner medium, cell cycle state, etc.), and the viruses affects to behaviour will develop the virus. The behaviours are: produce copies of the viruses (lytic state) or be inserted to the host genome and be silenced until dangers for the virus became (lysogenic state). The aim of this project is to develop new applications that allow controlling 𝛌-phage virus (bacteriophage) in several scenarios. The control was reached with synthetic genetic construct that interacts with the wild type genome of the virus in order to control the transition between the lysogenic and lytic states. This study was a computational approach where we use the simple model from Hasty [1] that describes CI-CRO genetic circuit, responsible of the virus bistability, and we add in this system the parts that describes our synthetic circuits. Using this approaches we have finally obtained circuits that make the bacteria immune to the 𝛌-phage virus infection, lyses the cells using an external effector and finally a population control of infected cells via coupling Quorum sensing [2] with the regulation of the viral genome. For all these systems we have agent-based simulations using Netlogo. These simulations and the simplicity of the synthetic circuits give us good perspectives in order to be implemented in the wet-lab.