That was it a long-standing enigma in biology: How do cells know how big they are?
The answer turned out to be hidden in Robert Sablowski’s computer files, collecting virtual dust since 2013. “I’ve had data for years and years, but I haven’t looked the right way,” says Sablowski, a plant cell biologist at the John Innes Center in Norwich, England. For an earlier project, he investigated a protein called KRP4. By combining with the fluorescent protein of jellyfish to make it shine, Sablowski could study it inside a plant cell, but he had no idea that this would be key to understanding cell size regulation.
In order for organisms to develop, their cells must go through a pattern of growth, DNA replication and division. But scientists studying this process, known as the cell cycle, have long noticed that divisions are not necessarily identical – cells often divide asymmetrically, and their size is later corrected. U study published in Science last month, Sablowski and his colleagues discovered how plants do it: cells use their own DNA as a kind of measuring cup. While the discovery was made by studying the so-called plant Arabidopsis, could have broad implications for understanding cell size regulation in animals and humans, and could even influence the future of crop production.
Identifying how cells estimate their own size was complex because most cellular proteins scale with the size of the cell itself. Sablowski compares the situation to trying to measure yourself with your own hand. “You can’t do that because your arm grows in proportion to your body,” he says. “You need an external reference to know how big you are.” However, what does not change with the growth of a cell is its DNA. Scientists have long speculated that a cell could use its DNA as a kind of indicator to measure its size, but Sablowski’s team was the first to show evidence of this process.
“For many, many decades, biology has been a profound mystery about how cells can accomplish this task almost magically knowing what their size is,” says Martin Howard of the John Innes Center, who helped develop the mathematical models needed for the breakthrough. Shape and size regulation are important because they are closely related to the way a cell functions: Too large and a cell can find it difficult to quickly obtain the information contained in its own DNA; too small and the cell does not have enough space for proper cleavage, which causes errors in division and growth that could lead to disease.
Arabidopsis is actually a weed, according to Sablowski, but in plant biology it is considered an exemplary organism because it is easy to grow and matures quickly. This means that other researchers in this field have already studied it well. “Community for Arabidopsis was critical, ”says Marco D’Ario, a graduate student at the John Innes Center who designed and helped run the experiment. “The same experimental setup that took us three or four years – without the community it would easily have taken 10 to 15 years.”
The team grew Arabidopsis in pots for about six weeks, and then cut off the tiny top of the plant, the part where new leaves and flowers appear, to observe its continuous growth under a microscope. They could track, at a magnification of about 1000X, the location and size of each cell at the ascending peak at different stages of the cell cycle. Sablowski and D’Ario traded shifts, checking cells every other hour for two days. “We had the equipment, we had the material. We just had to roll up our sleeves and do a 48-hour experiment to get data that no one else had, ”says Sablowski.