The fruit fly scientists gathered on Crete for their biennial meeting in June. A Canadian geneticist was among them. Fruit flies are used to study evolution and development. The species Drosophila melanogaster, a winged workhorse that has served as an insect collaborating on at least a few Nobel Prizes in physiology and medicine, is most often chosen by such scientists.

Alternative species are also cultivated by Dr. Extavour. She is a big fan of the cricket, particularly the two-spotted field cricket, even though it does not yet enjoy anything like the fruit fly. Principal investigators applied to attend the meeting in Crete.

She swatted away a beetle while in her hotel room. There could be five or 10 heads of labs working on that cricket species.

Crickets have been used as disease models and pharmaceutical factories. It is possible to haveitable polymaths. They are becoming more popular as food, chocolate covered or not. Crickets have more in common with other insects than fruit flies, which is why they offer more opportunities to learn. More than 85% of animal species are made up of insects.

ImageCassandra Extavour, a principal investigator on the study, in her office at Harvard University. “We should pick the right tool, and that includes the right organism, for the sort of question we want to ask,” she said.
Cassandra Extavour, a principal investigator on the study, in her office at Harvard University. “We should pick the right tool, and that includes the right organism, for the sort of question we want to ask,” she said.Credit...Tony Luong for The New York Times
Cassandra Extavour, a principal investigator on the study, in her office at Harvard University. “We should pick the right tool, and that includes the right organism, for the sort of question we want to ask,” she said.
ImageNotebooks and a plate of crickets in Seth Donoughe’s home lab near the University of Chicago. He described embryology as the study of how a developing animal makes “the right parts at the right place at the right time.”
Notebooks and a plate of crickets in Seth Donoughe’s home lab near the University of Chicago. He described embryology as the study of how a developing animal makes “the right parts at the right place at the right time.”Credit...Mustafa Hussain for The New York Times
Notebooks and a plate of crickets in Seth Donoughe’s home lab near the University of Chicago. He described embryology as the study of how a developing animal makes “the right parts at the right place at the right time.”

Dr. Extavour wants to know how the embryo works. How the first animal came to be may be revealed by that. One cell becomes many, then they arrange themselves in a layer at the egg's surface, giving an early blueprint for all adult body parts. embryo cells have the same genome but aren't all doing the same thing, how do they know where to go and what to do

The mystery is for Dr. Extavour. I want to go to that place.

embryology is the study of how a developing animal makes the right parts at the right time. Dr. Extavour, Dr. Donoughe and their colleagues found that good old fashioned geometry plays a starring role.

Humans, Frogs, and many other animals start as a single cell and then divide again and again into different cells. In crickets and most other insects, the nucleus of the cell is the only part of the cell that can change.

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A time-lapse video of two cricket embryos inside their respective eggs, captured during a five-day period of their development. Video by Seth Donoughe

The fruit fly's nucleus is carried along by flows in the cytoplasm, similar to leaves moving on a stream.

The cricket embryo had something going for it. The researchers spent hours watching and analyzing the dance of nuclei, which were glowing nubs dividing and moving in a puzzling pattern, not altogether orderly, not quite random, at varying directions and speeds. The performance was more than just physics.

The geometries that the nuclei assume are the result of their ability to sense and respond to other nuclei nearby. The new study was found to be moving by the doctor. He said it was a beautiful study of a beautiful system.

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Fluorescent cell nuclei dividing in the cricket embryo. Video by Taro Nakamura

The cricket researchers looked closely and paid attention to what they saw. The doctor said they just watched it.

They used a laser-light sheet microscope to take pictures of the nuclei every 90 seconds during the embryo's initial eight hours of development. Crickets hatch around two weeks.

Even with the most souped up microscope, biological material is hard to see. Taro Nakamura, now a developmental biologist at the National Institute for Basic Biology in Japan, engineered crickets that glowed fluorescent green. The results of the embryo's development were "astounding."

The exploratory process began at that point. When you discover something, you may not say "Eureka!", but you may say "Huh". It's weird.

The biologists watched the videos on loop, projected onto a conference-room screen, because the embryos are about one-third the size of rice. The data sets were overwhelming. They need to be more quantitative.

A mathematician at the University of Wisconsin-Madison was shown the dancing nucleus by Dr. Donoughe. It was 'WOW!'. The doctor said, Dr. The potential for a data-powered collaboration was something he had never seen before.

The math-bio team had a lot of questions to ponder. They started to divide. How were they going to get there? What location did they end up in? People were crawling and some were zipping around.

ImageJordan Hoffmann helped to identify higher-order geometric patterns in the movements of the nuclei.
Jordan Hoffmann helped to identify higher-order geometric patterns in the movements of the nuclei.Credit...Tom Jamieson for The New York Times
Jordan Hoffmann helped to identify higher-order geometric patterns in the movements of the nuclei.
ImageDr. Donoughe, a biologist and data scientist, enjoys “thinking about the spacing of cells, the sizes of cells, the shapes of cells.”
Dr. Donoughe, a biologist and data scientist, enjoys “thinking about the spacing of cells, the sizes of cells, the shapes of cells.”Credit...Mustafa Hussain for The New York Times
Dr. Donoughe, a biologist and data scientist, enjoys “thinking about the spacing of cells, the sizes of cells, the shapes of cells.”
ImageTaro Nakamura engineered a strain of crickets with nuclei that glowed fluorescent green.
Taro Nakamura engineered a strain of crickets with nuclei that glowed fluorescent green.Credit...Kosuke Okahara for The New York Times
Taro Nakamura engineered a strain of crickets with nuclei that glowed fluorescent green.
ImageChristopher Rycroft, an applied mathematician at the University of Wisconsin-Madison and a principal investigator on the new study.
Christopher Rycroft, an applied mathematician at the University of Wisconsin-Madison and a principal investigator on the new study.Credit...Tony Luong for The New York Times
Christopher Rycroft, an applied mathematician at the University of Wisconsin-Madison and a principal investigator on the new study.

At the intersection of the life and physical sciences, Dr. He wrote about the physics of paper crumpling. He said that math and physics have had a lot of success in creating general rules that apply broadly.

The team spent a lot of time at a white board. A Voronoi diagram is a geometric construction that divides a space into nonoverlapping subregions that each originate from a seed point. It can be applied to things as diverse as the growth pattern of forest canopies, as well as the different types of wireless networks. The tree trunks are the seed points and the crowns are the cells that are not encroaching on one another.

The researchers observed that the cell's shape helped predict the direction the nucleus would go next. According to Dr. Donoughe, Nuclei moved into nearby open space.

He said that geometry offers a way to think about cellular mechanics. Even though it was obvious that the mechanical forces were at play, we couldn't directly measure or observe them. Higher-order geometric patterns can be observed by researchers. The spacing of cells, the sizes of cells, the shapes of cells come from mechanical constraints, according to Dr. Donoughe.

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A simulation of cell nuclei dividing and moving within the cricket egg. Each colored blob represents the space around each nucleus. Video by Jordan Hoffmann

The cricket videos gave Dr. Donoughe and Dr. Hoffmann a lot of information.

A lot of forms of computer vision and machine- learning are involved in this process.

They clicked through 100,000 positions to verify the results of the software. It was tedious and Dr. Donoughe thought of it as a video game.

They created a model that tested and compared hypotheses about the movement of the nucleus. They didn't find the flows that Dr. Di Talia saw in the fly. Random motion and the idea that nuclei pushed each other apart were found to be false.

The mechanism in fruit fly and roundworm embryos that extend clusters of microtubules is similar to a forest canopy.

The cricket nuclei were drawn into the empty space by a similar kind of force. Dr. Extavour said in an email that they don't know if the molecule is microtubule or not. In the future, we will have to do more experiments to find out.

ImageDr. Donoughe’s “embryo-constriction device.”
Dr. Donoughe’s “embryo-constriction device.”Credit...Seth Donoughe
Dr. Donoughe’s “embryo-constriction device.”

This cricket odyssey is incomplete without mentioning Dr. Donoughe's custom-made embryo-constriction device. It was inspired by work done with Dr. Extavour on the evolution of egg sizes and shapes.

Dr. Donoughe was able to perform the task of looping a human hair around a cricket egg by using this contraption.

The researchers looked at the nuclear dance. The nuclei slowed down in the original area. When a few nuclei sneaked through the tunnel, they sped up again and let loose like horses.

This was the strongest evidence to date that the movement of the nucleus was governed by geometry.

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Fluorescent nuclei in a cricket embryo that has been constricted by a human hair. Video by Seth Donoughe

By the end of the study, the team had accumulated more than 40 terabytes of data on 10 hard drives and had refined a Computational, Geometric model that added to the cricket's tool kit.

Dr. Extavour wants to make cricket embryos more versatile to work with in the laboratory.

Dr. Extavour said that the model could be used as a testing ground for other insect embryo. She said that it will be possible to compare diverse species.

The collaborative spirit was the greatest reward of the study.

There is time for specialized knowledge. We need to expose ourselves to people who aren't as invested as we are in any particular outcome

The questions posed by the mathematicians were not prejudiced. Those are the most interesting questions.