All life on Earth is made up of cells. We don't know how the simplest of those cells function.
The most complete computer simulation of a living cell has been created by a team at the University of Illinois. With this digital model biologists can explore how the most basic unit of life ticks and what would happen if it changed.
The senior author, Zaida (Zan) Luthey-Schulten, said that it would take many, many experiments to recover results from one simulation. Using the model, she and her colleagues have already made surprising discoveries about the physiology and reproductive cycle of their modeled cell, and the simulation continues to serve as an idea generator for further experiments.
Kate Adamala said that this is the first time that a careful computational look into a metabolism of a whole complex system is possible. It's hard to build a model if you don't know what.
The cell that the Illinois group is working with is so simple, with far fewer genes than any other cell, that it is an ideal platform for a model.
A lab-made cell teeters on the line between life and non-life, carrying a limited number of genes, most of them necessary for survival. By replicating the biochemical processes happening inside this very basic cell and tracking all the nutrients, waste, gene products and other molecule moving through it in three dimensions, the simulation brings scientists closer to understanding how the simplest life form sustains itself and reveals some of the bare-bones requirements of life.
Building models of natural cells that are more complex and significant is what the findings are about. Adamala said that if scientists could build an equally detailed simulation of the common intestinal bacterium Escherichia coli, it would be an absolute game-changer.
An updated version of a cell developed by synthetic biologists at the J. Craig Venter Institute was presented in Science in 2016 The project's scientists stripped genes that were not essential for life in order to design its genome. The JCVI-Syn3A has 493 genes, less than half of the number of genes that E. coli has.
The cell is simple, but not clear. No one knows what 94 genes do except that the cell dies. John Glass, a co-author of the new study and the leader of the synthetic biology group, said that their presence suggests that there may be living tasks or functions essential for life. The researchers hope that with modeling they can quickly uncover some of the mysteries.
This is the first time that we can look into the metabolism of a whole complex system, not just a biochemical reaction or a very artificial system.
Kate Adamala is a student at the University of Minnesota.
The team at the University of Illinois took a lot of findings from different fields and wove them together to create a new model. The images of the minimal cell were used to position the machinery. A detailed analysis of the cell's chemical composition, provided by their co-authors at the Dresden University of Technology in Germany, helped them place the right molecule on the outside. A map of the cell's biochemistry provided a guide for the interactions of the molecule.
As the digital cell grew, thousands of simulations of biochemical reactions occurred, showing how each molecule changed over time.
Living JCVI-Syn3A cells were mirrored in the simulations. They predicted how the cell splits out its energy budget and how quickly it degrades, two things that are critical to understanding how the cell regulates genes.
The rapid growth and division of JCVI-Syn3A cells were some of the most surprising discoveries. The simulation showed that the cell needs a transaldolase to divide quickly, but it doesn't seem to have one. Either the cell has evolved a metabolic pathway that makes the enzyme unnecessary, or we are left with the possibility that it does not look like an ordinary transaldolase.
He and his team are trying to find a mystery molecule while also testing some of the model's other predictions. Adding genes for two non essential enzymes can shorten the time between cell divisions.
The model has important gaps, such as the unknown functions of 94 genes, and not all of the simulation's data agreed with experimental data. To fully understand the cell, we need to model all of the forces and interactions of every atom or molecule of the cell.
He is talking to Roseanna Zia, an associate professor of chemical engineering atSTANFORD University, about building biophysical models of JCVI-Syn3A that would examine how physics drives interactions inside the cells.
Elizabeth Strychalski, who heads the cellular engineering group at the National, said that the study is so ambitious that it is difficult to do.
The researchers should be able to get creative with a complete enough model, as they can see what happens if they drop in extra molecule or set the simulation in a different environment. The results will give more insight into which processes cells need to survive. They could offer a glimpse into what the first cells needed.
Luthey-Schulten and her team hope to use the model to investigate deeper questions about the minimum principles of life. They are sifting through the data that the model has already provided.
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