Artificial Cells Produce Real Proteins


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A living cell, from one point of view, is a sort of sprawling protein factory that can churn out thousands of different proteins to order. Prof. Roy Bar-Ziv of the Weizmann Institute’s Materials and Interfaces Department is building on the basic idea of creating “artificial cells” that might, in the future, enable us to control the production of proteins or other complex biological processes.

Fluorescent image of DNA (white squares) patterned in circular compartments connected by capillary tubes to the cell-free extract flowing in the channel at bottom. Compartments are 100 micrometers in diameter



The system, designed by PhD students Eyal Karzbrun and Alexandra Tayar in Bar-Ziv’s lab, in collaboration with Prof. Vincent Noireaux of the University of Minnesota, comprises multiple compartments etched onto a biochip. These tiny artificial cells, each a mere millionth of a meter in depth, are connected via thin capillary tubes, creating a network that allows the diffusion of biological substances throughout the system. The instructions – DNA designed by the scientists – are inserted into the cells, along with the protein-making machinery and raw materials – both provided by an extract of the bacterium E. coli.

The genetic sequence the researchers had inserted contained two regulatory genes – basically “on” and “off” switches. Much like their real counterparts, the artificial cells are linked through a capillary system to a feeding channel that enabled them to absorb nutrients and exchange materials; and they, in turn, created proteins in a periodic fashion.

(l-r) Eyal Karzbrun, Alexandra Tayar and Prof. Roy Bar-Ziv
The network also mimicked a key facet of complex cellular communication – one that takes place during embryonic development. As the body plan takes shape – a process called morphogenesis – the diffusion of proteins out of the cells becomes crucial. Tayar: “We observed that when we place a gene in a compartment at the edge of the array, it creates a diminishing protein concentration gradient; other compartments within the array can sense and respond to this gradient – resembling an embryo during early development. We are now working to expand the system and to introduce gene networks that will mimic pattern formation, such as the striped patterns that appear during fly embryogenesis.”
Bar-Ziv: “Genes are like Lego in which you can mix and match various components to produce different outcomes; you can take a regulatory element from E. coli that naturally controls gene X, and produce a known protein; or you can take the same regulatory element but connect it to gene Y to get different functions that do not naturally occur in nature.” This research may, in the future, help advance the synthesis of such things as fuel, pharmaceuticals, chemicals and the production of enzymes for industrial use, to name a few of the possibilities.
Prof. Roy Bar Ziv's research is supported by the Yeda-Sela Center for Basic Research.