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The most complete simulation of the hidden rules in life of Cell Probe


Strange word organisms on the ocean floor to the bacteria inside our bodies, all life on Earth is composed of cells. But we only have a very rough idea of ​​how even the simplest cells work.

Now, like recently described in Cabinet, a research team at the University of Illinois, Urbana-Champaign and their colleagues have created the most complete computer simulation ever of a living cell. With this digital model, biologists can overcome the constraints of nature and accelerate discovery of how the most basic unit of life works — and what if it operate differently.

“Imagine being able from a simulation…recover results that would take a lot of experimentation to do,” said the senior author, Zaida (Zan) Luthey-Schulten, who led the team that performed the simulations at the University of Illinois. Using this model, she and her colleagues made surprising discoveries about the physiology and reproductive cycle of their modeled cells, and simulations continue to serve as a source of ideas. for further experiments.

“For the first time, we have been able to have a really careful computational look at the metabolism of an entire complex system — not just a biochemical reaction or an artificial system, but the entire system. living cells,” says Kate Adamala, a synthetic biologist and assistant professor at the University of Minnesota, who was not involved in the study. For years, scientists have tried to model whole cells and accurately predict their biology, but they have failed because most cells are too complex. “It’s hard to build a model if you don’t know the Lego bricks that make it up,” says Adamala.

But the cell the Illinois team is working with is so simple, with fewer genes than any other, that its physiology is susceptible to deterioration, making it the ideal foundation for a model.

The cell in question is a “minimum cell” created by a laboratory that the boundary between the living and the non-living, carries a limited number of genes, most of which are necessary for existence. By recreating the known biochemical processes that occur inside this very basic cell and keeping track of all the nutrients, waste products, gene products and other molecules moving through it in three-dimensional space. dimension, simulation brings scientists closer to understanding the simplest way of life that is self-sustaining and reveals some of life’s bare requirements.

This discovery is a stepping stone to building more complex and meaningful models of natural cells. If scientists can finally build an equally detailed simulation of common gut bacteria Escherichia colifor example, “that would be an absolute game changer, because all of our bio feng shui production runs on E coli“Adamala said.

A digital life

The minimum cell that the team modeled, JCVI-syn3Ais an updated version of one developed by synthetic biologists at the J. Craig Venter Institute and presented in Science in 2016. Its genome was designed based on a very simple bacterial genome Mycoplasmas mycoides, but removed the genes that the project’s scientists had systematically identified as not essential for life. JCVI-syn3A grows with just 493 genes, almost half the number of bacteria that inspired it and only about one-eighth as many genes. E coli Yes.

Although simple, the cell is still very mysterious. For example, no one knows what 94 of those genes do except that cells die without them. Their presence suggests that there may be “necessary life functions or tasks that… science is forgetting,” says John GlassCo-author of the new study, led the synthetic biology team at the Venter Institute, and was part of the minimal cell development group in 2016. With the modeling, the researchers hope they can Quickly uncover some of these mysteries.



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