Charting the way to minimal cells

Ironically, the closer we get to building a living cell, the less we are able to understand it. During the three-day virtual workshop “Reconstituting biology - charting the way to minimal cells”, cell-building researchers agreed this complexity is what makes cells so interesting. 

A group of 35 synthetic cell researchers from three different continents got together virtually at the Lorentz workshop from 29th June till 1st July, to reflect on the achievements and promises of bottom-up synthetic biology worldwide. In the bottom-up approach to making a synthetic cell, researchers reconstitute an aspect of the cell in vitro – outside of the living system. Over the last five years a lot of progress has been made with this technique on how cell systems work.

Proteins reveal hidden functions
As it turns out, proteins reveal new, previously hidden functions when you build them from the bottom up, outside of their natural environment. These new functions might actually be quite old, Professor Petra Schwille from Max Planck Institute of Biochemistry shares during the discussions: “Life on earth is a constantly evolving process. The very first cells looked completely different from what they look like now. They competed with other living systems and so accumulated functions through time. Proteins show functionality that very early predecessors of molecules might have had long ago.”

How is it possible that a protein shows more function outside of its natural home? Dr. Schwille uses a remarkable analogy to explain this: “Let’s say an alien would study us, and think the function of a human is pressing buttons because it observes the person using a dishwasher. Remove the dishwasher though, and the person can still do the dishes by hand. But an alien wouldn’t know this, because the person is not doing it.” In the same way that humans act differently depending on their environment, a protein outside of a cell is free to unfold its functionality in different ways.

The more we build, the less we understand
How can mechanistic discoveries in these simpler systems help us understand the synthetic cell as a whole? Nathan Gaut from the University of Minnesota describes the challenges the research community faces: “In the last two decades we started to understand how processes work within a cell. Now we are able to constitute singular cell processes outside of the cell. The main challenge at the moment is how to couple those two together.”  

The surprising functionality found in proteins may help us towards sustainable solutions, like zero-waste production and self-healing materials. The participants agree that to build a synthetic cell, we don’t need to understand it. In fact the opposite seems to be the case: the closer we come to what constitutes a living cell, the less we are able to understand how the cell works. There is one thing the cell-builders know for sure, though: if the cell wasn’t so complex, it wouldn’t be so interesting.