News Desk | Illinois

Champaign, Illinois – Scientists report that they’ve built a living “small cell” with a genome stripped to its lowest essentials – and a computer model of the cell that mirrors its behavior. By improving and testing their model, the scientists say they are developing a system that can predict how changes to the genome, living conditions or physical properties of living cells will alter the way they function.

They report their findings in the journal Cell.

Small cells have reduced genomes that carry the genes needed to replicate their DNA, grow, divide, and perform most of the other functions that define life, said plus (Zann) Luthy Schulten, a professor of chemistry at the University of Illinois at Urbana. Champagne who led the work with graduate student Zane Thornberg. “What’s new here is that we have developed a fully dynamic 3D kinematic model of a small living cell that simulates what happens in an actual cell,” said Lothi Schulten.

The simulation maps the exact location and chemical properties of thousands of cellular components in three-dimensional space at the atomic scale. It keeps track of how long it takes for these molecules to travel through the cell and meet each other, what kinds of chemical reactions take place when they occur, and how much energy is required for each step.

To build the minimum number of cells, scientists at the J. Craig Venter Institute in La Jolla, California, have turned to the simplest living cells – mycoplasma, a genus of bacteria that parasitize other organisms. In previous studies, the JCVI team built an artificial genome missing as many nonessential genes as possible and grew the cell in an environment rich in all the nutrients and factors needed to maintain it. For the new study, the team added a few more genes to improve cell viability. This cell is simpler than any naturally occurring cell, which makes it easy to design on a computer.

Simulating something as massive and complex as a living cell relies on data from decades of research, said Lothi Schulten. To build the computer model, she and her colleagues in Illinois had to calculate the physical and chemical properties of a cell’s DNA; Fats. Amino acids; and machinery for gene transcription, translation, and protein synthesis. They also had to model how each component propagated through the cell, keeping track of the energy required for each step in the cell’s life cycle. NVIDIA GPUs were used to run the simulations.

“We built a computer model based on what we know about the small cell, and then ran simulations,” Thornberg said. “And we checked whether our simulated cell behaves like the real thing.”

Luthi Schulten said the simulations gave the researchers insight into how the “actual cell balances the demands of metabolism, genetic processes and growth.” For example, the model revealed that the cell uses the bulk of its energy to import ions and essential molecules across the cell membrane. This makes sense, said Lothi Schulten, because mycoplasma gets most of what it needs to survive from other organisms.

The simulations also allowed Thornburg to calculate the normal lifespan of messenger RNA, the genetic blueprints for building proteins. They also revealed a relationship between the rate of synthesis of lipids and membrane proteins and changes in membrane surface area and cell volume.

“We simulated all the chemical reactions inside a small cell – from its birth to the time it divides two hours later,” Thornberg said. “From this, we get a model that tells us about cell behavior and how we can complicate it to change its behaviour.”

“We have developed a fully 3D kinetic and dynamic model of a small living cell,” said Lothi Schulten. “Our model opens a window into the inner workings of the cell, showing us how all components interact and change in response to internal and external signals. This model—and other, more complex models in the future—will help us better understand the basic principles of life.”

Luthi Schulten holds the Murchison Mallory Chair in Chemistry. She is a professor of physics and a member of the Beckmann Institute for Advanced Science and Technology, Karl. R. Woese Institute for Genomic Biology, Center for Biophysics and Quantum Biology and Theoretical and Computational Biophysics Group in the United States. She is also co-director of the National Science Foundation Center for Living Cell Physics in Illinois.

The National Science Foundation and the National Institutes of Health support this research.

Leave a Comment