Whether bacterial or archaeal, all happy families are alike

An archaeon uses the same strategy as several other microbes to time cell divisions.

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The corresponding Nature Microbiology paper is here: http://go.nature.com/2z8EjTO 

The following authors of the paper contributed to writing this blog: Po-Yi Ho, Dr. Amy Schmid, Dr. Ethan Garner, and Dr. Ariel Amir.

Four decades have elapsed since the proposal to give archaea their own branch in the tree of life. Nevertheless, our understanding of archaeal physiology is far behind that of bacteria or eukaryotes, and many surprises are likely still waiting to be revealed. One fundamental outstanding problem has been the molecular mechanisms underlying growth. For example, how does cell volume expand over time? When and how do cells commit to cell division? Dr. Yejin Eun et al. set out to investigate some of these questions in Halobacterium salinarum, an experimentally tractable archaeal species. This organism is found in nature in salt lakes like the Great Salt Lake in Utah, USA, and the Dead Sea in Israel. It needs nearly saturated salt to grow.

The first step used in our work was to develop a systematic method to visualize the single growth of H. salinarum. Although H. salinarum can double in mass in only six hours with optimum nutritional conditions, its need for salt makes it incredibly challenging grow on a microscope slide. Standard methods for microscopy fail because the water in the growth medium evaporates in minutes, leaving nothing but salt crystals behind. To make matters worse, these archaea are “softer” than the more rigid bacteria, so standard microscopic slides or microfluidic chambers cause them to flatten or break. To overcome these difficulties, we developed specialized growth microchambers that allowed us to track single cells as they grow for up to eight cell divisions per chamber, without affecting their shape. Dr. Eun perfected this protocol over two years, creating a systematic method allowing the visualization and quantification the growth of single cells of H. salinarum and other “fragile” microbes.

With this setup in hand, we were able to conduct quantitative analysis on single-cell growth data to answer the above questions. We found that archaeal cell volume grows exponentially in time at the single-cell level. By creating a mathematical model of growth based on our data, we found that cells add a constant size from birth to division, regardless of how large they are at birth. We demonstrate that our data and model are consistent with the so-called “adder” model of cell division. The strategy leaves a distinct signature: the correlation coefficient between the size at birth of a mother cell and that of the daughter cell is one half. This finding was striking because many bacteria and even baker’s yeast use the same cell division strategy even though billions of years of evolution separate these organisms.

Our data also revealed unique features of archaeal cell division. Even though archaeal cells, on average, both grow exponentially and divide in the middle, the location of the division plane and the rate of growth are more variable from cell to cell what is observed for bacteria. We incorporated these additional variabilities to create a unified model of cell division regulation that can quantitatively explain the statistics of our data. Our model shows that, despite these variabilities in growth and division, the correlation between mother and daughter cell sizes within the adder model remains the same. In other words, this correlation is a robust hallmark which defines the cell division strategy.

Whether bacterial, fungal, or archaeal, all mother-daughter correlations are alike for most happily growing cells. It may be that the adder strategy is a general guiding principle of cell growth and division across all life, and we will find out as growth of more diverse organisms is examined. Stay tuned for future research results!

Header photo: Halobacterium salinarum growing on salt crystals. Photo by Alex Bisson.

Po-Yi Ho

Graduate researcher, Harvard University