Researchers from the Structural Bioinformatics and Network Biology Lab, led by Dr. Patrick Aloy at IRB Barcelona in PCB, have published in Science the first study to evaluate how environmental conditions affect the genetic program underlying cellular survival. The work builds on previous research on yeast cells, which are similar to human ones but they are easier to study because they have smaller genomes and there are well-established techniques for their genetic manipulation.

Cells are more resilient to environmental perturbations than previously thought. Observations of the effects of drugs or mutations on cells grown in a lab setting indicate that they overcome external influences and provide a solid basis for developing new diagnostics and treatments.

A group of researchers, including ICREA researcher Dr. Patrick Aloy, head of the Structural Bioinformatics and Network Biology lab at IRB Barcelona, and Dr. Carles Pons, Ramón y Cajal research associate in the same lab, have published a study in the journal Science showing that Baker’s yeast cells use the same gene interaction network to coordinate growth in response to a wide range of environments.

“We wanted to test in an unbiased way how the reference genetic network of a model cell changes in different environments,” says Dr. Brenda Andrews, former director of the Donnelly Centre who co-led the research. “And we found that the network is highly resilient and remains broadly the same, which means that a single reference condition provides us with a nearly complete view of the molecular wiring of a cell.” Dr. Charles Boone,  Professor of Molecular Genetics and interim Director of the centre, and Dr. Chad Myers, professor of computer science at the University of Minnesota-Twin Cities, were also senior authors of the paper.

“We have contributed to this work by characterizing the responsive genes to environmental changes and by analysing the functional coherence of the discovered genetic interactions in the different tested conditions” says Dr. Aloy.

The work builds on previous research that established how yeast’s ~6000 genes form a network of ~900,000 interactions. Yeast cells are similar to human ones but they are easier to study because they have smaller genomes and there are well-established techniques for their genetic manipulation. This explains why scientists have been using these cells as a research model to study the molecular foundations of life.

“As the only genome-wide map of genetic interactions for any cell, the global yeast genetic network is a unique reference resource. The interactions between genes provide clues about their function, and they can also reveal how mutations combine to cause the cellular defects underlying diseases,” says Dr. Pons. “A robust reference map is also key for identifying the best genes to target therapeutically,” he adds.

There was concern, however, that genes might change their interacting partners depending on the cellular environment, which would complicate things because it would mean that the molecular wiring is dynamic, like a moving target. The reference map was constructed from data collected under standard laboratory conditions, but alteration of the conditions may affect the network.

Others have reported that the environment can rewire the interactions within a select group of genes involved in a specific cellular process, such as DNA repair, but its impact across the genome had not been assessed systematically.

» Reference article:  Costanzo, Michael et al. (2021), Environmental robustness of the global yeast genetic interaction network, Dryad, Dataset. DOI: 10.1126/science.abf8424

» For further information: IRB Barcelona website [+]