Biology – the study of living things – can admittedly be a little reductive at times.
It's easy to miss important connections depending on how you look at an organism. Microscopes show us the fine details of a body, dissection has helped us identify different organs, and X-rays can show us the bigger picture of internal systems.
But until now, it's been tricky to see how living cells communicate across those systems, which traditionally have been studied in isolation, even though our bodies ultimately work as a whole.
Now, scientists have figured out how to watch cells from disparate parts of the body communicate with each other. Their research has been presented in the journal Nature.
"This work bridges two fundamental scales of biology – the cell and the organism – such that we can now fill that observability gap," says computational neuroscientist Virginie Ruetten, who developed the technique along with a team based at the Howard Hughes Medical Institute in the US.
"There are some really basic properties that were just missing because it's been very difficult to look at cellular responses at scale."
The new imaging technique – dubbed WHOLISTIC (WHole-Organism Live-Imaging System for recording Tissue and IntraCellular activity) – captures cellular activity across the entire body, second by second.
So far, Ruetten and team have used this technique to image real-time signaling in naturally transparent animals: first with larval zebrafish, and then with another kind of freshwater fish, Danionella cerebrum, which remain transparent into adulthood.
Both of these fish are important model organisms in scientific research.
Being able to see how the cells in their bodies communicate across different organ systems could help scientists figure out how similar systems in our own bodies might be working, too.
Calcium is a near-universal signal cells use to communicate with each other. It's involved in all manner of biological processes. It helps muscles to contract and synapses to fire; it's crucial at the start of life, when sex cells are fertilized, and at the end, when cells are programmed for death.
The WHOLISTIC technique uses genetic engineering to make nearly every cell in the body express fluorescent calcium sensors. These sensors literally light up when calcium levels in the cells shift.
"We know that evolution has produced functioning organisms, but evolution didn't care whether a decision was implemented in the brain's prefrontal cortex or in a connection between the brain stem and the bladder," says neuroscientist Misha Ahrens, whose lab hosted the research.
"This now allows all these fields – physiology, neuroscience, behavior, cell biology – to connect and study all of them in the same animal."
This whole-body imaging approach has already led to some unexpected findings.
For one, the scientists saw calcium sensors in a fish's chondrocytes (the main cells that form cartilage) flaring up in response to the cold.
They were also surprised to see the brain's protective tissue layers (meninges) – not just its neurons – responding to ketamine.
Zooming out, the body's rhythms were illuminated like never before.
"At the multi-organ scale, it revealed unknown muscle synergies and muscle–organ interactions," the authors report in their paper.
"At the whole-organism scale, the method captured brainstem-controlled redistribution of body-wide blood flow."
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The team hopes that scientists around the world will be able to adopt this method for their own research, offering unprecedented insight into the body as a whole.
The research is published in Nature.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.