Synthetic Cellular Organelles Engineered

According to a paper published in Science today, the complex biological process of translation has been engineered into a designer organelle in a living mammalian cell. An EMBL-led team used this technique to create a membraneless organelle that can build proteins from natural and synthetic amino acids carrying new functionality. This capability will allow scientists to study, tailor, and control cellular function in more detail.

"Our tool can be used to engineer translation, but potentially also other cellular processes like transcription and post-translational modifications. This might even allow us to engineer new types of organelles that extend the functional repertoire of natural complex living systems," explains Christopher Reinkemeier, Ph.D. student and co-first author of the paper. "We could for example incorporate fluorescent building blocks that allow a glimpse inside the cell using imaging methods."

"The organelle can make proteins by using synthetic non-canonical amino acids. Currently we know of more than 300 different non-canonical amino acids—compared to 20 that are naturally occurring. We are no longer restricted to the latter ones," says co-first author Gemma Estrada Girona. "The novelty we introduce is the ability to use these in a confined space, the organelle, which minimises the effects on the host."

Translation is such a complex process that it cannot be contained in one single organelle surrounded by a membrane. Therefore, inspiration was drawn from phase separation, which is used by cells to locally concentrate specific proteins and RNAs. Even though these wall-less organelles have wobbly boundaries as they dynamically interact with the surrounding cytoplasm, they can still do very precise tasks. The team combined phase separation with cellular targeting to create their membraneless organelle and to make sure that only one organelle per cell is formed.

In the end, only five new components have to be engineered into a cell to build it. The assembly of these components generates a large structure, which might create some burden on the cell. In the future, the group aims to engineer minimal designer organelles, to minimize any impact on the physiology of the healthy organism.

Image: The authors see the newly developed synthetic host as a city. On one hand, typical cellular processes—seen as encapsulated, isolated, and made up of non-interchangeable elements—are represented as repetitive structures: squared, isolated blocks which are always fenced, just like membranous organelles. On the other hand, the image highlights the making of a new organelle—a new building that is not fenced, which is accessible to the rest of the city while having its own identity, a building that is more dynamic and flexible. Image courtesy of Gemma Estrada Girona.