A PROTO-ORGANELLE IN OPERATION: Stimulation of a light sensor on the membrane of a proto-organelle (1) leads to the transport of lactose from the organelle to the main compartment of the protocell. (2) The increase in lactose concentration prompts the release of a transcriptional repressor, LacI, (3) and the subsequent expression of enhanced green fluorescent protein. (4)© GEORGE RETSECK

The development of synthetic cells is in its infancy, and researchers are tackling the challenge from two angles. They can either modify an existing single-cell organism—for example, a bacterium—or start from scratch and build a membrane-encapsulated protocell. One major improvement to the latter approach, accomplished by David Miller, a researcher at the Walter and Eliza Hall Institute for Medical Research in Parkville, Australia, and his colleagues, is to add synthetic organelles.

“The advantage of using this bottom-up system is that you basically don’t have a lot of the evolutionary...

Existing protocell designs have consisted of a simple lipid membrane separating the inside of the cell and the reactions therein from the outside environment. But, “our idea was to add an additional lipid-bound compartment that would segregate some of the components,” explains Miller. He calls the compartment a proto-organelle.

Miller’s newly designed protocells have a single type of proto-organelle, a proof-of-concept structure containing lactose and a light-activatable transporter mechanism. In response to light stimulation the proto-organelles release lactose into the main protocell compartment, the equivalent of a cell’s cytoplasm, which contains a lactose-activated gene that encodes a fluorescent protein. The gene’s expression is tightly linked to the activity of the organelle, a level of control not previously possible in protocells.

By segregating further reactions and control mechanisms in a variety of proto-organelles, says Miller, “you could generate surprisingly complex behaviors from very simple component parts.” (J R Soc Interface, doi:10.1098/rsif.2013.0496, 2013)

Modify existing organisms Synthesize all or part of the genome from an existing bacterium. Rapid replication Bacteria already have pathways and processes in place. The organism’s existing biology may interfere with the desired reaction.
Build cells from scratch Create a lipid-encapsulated protocell. No replication, so researchers must replenish stocks With proto-organelles, multiple reactions can be segregated and controlled. It’s inevitably difficult to reconstruct what evolution has been perfecting since the dawn of cellular life.


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