Bangalore-based researchers have shown that simple biochemical processes drive single-celled organisms to differentiate and become varied communities of cells having different metabolism. This study can help us understand how multicellularity develops.
The group studied the common baker’s yeast (Saccharomyces cerevisiae) to show how multicellularity can emerge in single-celled microbes due to merely biochemical effects. The experiment starts with yeast cells that are similar in all respects — they all produce a sugar (trehalose) from available raw materials. As the colonies mature and the concentration of trehalose increases, some of the cells start using up the sugar, thereby slowly bringing about a balance in the concentration of trehalose. In the process, this results in the development of cells with two different types of metabolism – cells that produce trehalose and those that use up trehalose. These new cells are confined geographically to some areas within the colony. Such characteristics are necessary for the development of multicellularity. The study has been published in the journal eLife.
When the colony was allowed to mature, the researchers found that the cells with different properties formed into groups across the colony.
Light and dark cells
“We just arbitrarily called these cells 'light' and 'dark' based on how they appeared under a light microscope,” says Sriram Varahan of Institute of Stem Cell Science and Regenerative Medicine (inStem), Bengaluru. “Subsequently, with more characterisation, we found that these cells have very different metabolism and properties,” he adds.
The researchers integrated three different approaches. Sunil Laxman of inStem explains: “We used many microscopic approaches to characterise the cells. We also used highly sensitive analytical chemistry approaches (mass spectrometry) to identify all the metabolic processes, and show that this new sugar is made, builds up, and then when used by some cells helps them to switch to a new state.”
Mass spectrometry
As the team had small quantities of experimental material, they used mass spectrometry to analyse and differentiate between the different types of cells.
“Our collaborators Dr. Sandeep Krishna and Vaibhhav Sinha from National Centre for Biological Sciences made a theoretical model that can predict this entire colony development, using these biochemical processes,” says Dr Laxman.
Many microbes can form biofilms, in which cells with different properties are together in a group. These biofilms play a role in many diseases caused by bacteria and fungi. This study explains how such biofilms can form, suggesting a means to control the growth of biofilms.
The study has thrown open several questions for the team. “We need to figure out how cells put out this sugar; how cells start to break down the trehalose; whether a minimum number of cells is needed for this to happen,” says Dr Laxman.
