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)
| SYNTHETIC APPROACH | METHOD | GROWTH | ADVANTAGES | DISADVANTAGES |
| 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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