PNNL and Illinois build first 4D whole-cell model of photosynthetic bacterium Prochlorococcus MED4
Researchers combined cryo-electron tomography, time-series data and simulations into a model of a light-driven cell. It shows how the microbe keeps stable function as light changes.
A team led by Margaret Cheung, a computational scientist at Pacific Northwest National Laboratory (PNNL), together with the University of Illinois Urbana-Champaign, has built the first four-dimensional whole-cell model of a photosynthetic bacterial cell. The work was published in the Biophysical Journal, according to the release on newswise.com newswise.com
newswise.comnewswise.comOpen source ↗. The subject is the bacterium Prochlorococcus marinus MED4, which uses sunlight for energy.
The model links the cell's three-dimensional structure with changes in gene activity, proteins and metabolism over time. The authors say it could help develop computer simulations, plan laboratory experiments and reduce some of the trial and error in developing microbes for biotechnology.
How the model was built
The team used cryo-electron tomography, which produces three-dimensional images of frozen cells, to locate internal structures. These images mapped structures involved in capturing light, producing proteins and carrying out carbon fixation.
The researchers also collected coordinated time-series measurements of gene activity and proteins at matching times. MED4 cultures were studied as they shifted from darkness to light and from light to darkness. Cultures kept in constant darkness or light were examined too, which let the team separate immediate responses to light from changes controlled by the cell's internal clock newswise.com
newswise.comnewswise.comOpen source ↗.
Imaging and time-series data were combined with physics-based simulations of molecular activity across the cell. Large-scale computing resources supported these simulations. The authors state that the model and its dataset can be expanded and adapted to other photosynthetic microbes.
The CP12 switch and stability
The study found an important role for CP12, a small protein that helps regulate carbon fixation, the conversion of carbon dioxide into carbon-based molecules needed for growth. In darkness, CP12 joins with two carbon-fixation enzymes to form the "dark complex", which holds the enzymes inactive.
When light returns, chemical changes to CP12 and the enzymes cause the complex to break apart, releasing the enzymes so the cell can resume producing growth molecules. Because the switch acts on existing enzymes, it can adjust carbon fixation faster than processes that require changes in gene activity and new proteins newswise.com
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The model also showed that the locations of proteins and structures within the cell help reduce the effects of random variations in molecular activity. According to the authors, these controls together let the microbe respond to changing light while keeping cellular functions stable.
"Whole-cell models depend on experimental measurements that show what a cell is doing over time," said Zan Luthey-Schulten, a University of Illinois Urbana-Champaign chemistry professor and corresponding author. The release notes the model may inform future research in biotechnology, synthetic biology and biomanufacturing.
