The Driving Force

Suddenly it clicks, and a new idea is born. Marissa Scavuzzo knows the feeling. “It’s only when I am not pondering a specific problem in my laboratory that the best ideas come to me”, says the 36-year-old developmental biologist. This could happen when she is playing with her two-and-a-half-year-old daughter Lillo, or when she is out on a backpacking trip with her husband Andrew. Or in the case of her essay for the journal “Science”, during a car ride. She sent a voice message to herself to make sure nothing was forgotten, and once at home, she put it all in writing. During the award celebrations for the Eppendorf & Science Prize for Neurobiology on November 12, 2023, in Washington, Peter Stern, chairperson of the jury, emphasized that it was her “exceptional article” which made the difference to the jury and won her the award. Her essay carries the rather mysterious title “The Way You Move”.
Very soon, however, readers will learn which type of movement this is all about. An excerpt from the essay which convinced the jury: “Close your eyes and take a large drink of water. Pay attention to everything you feel as the water moves into your esophagus and down your throat. It takes conscious control and effort to move the water as you swallow. Then you can feel – but no longer control – the peristaltic wave in your esophagus as this organ takes over the action you consciously initiated. But soon after, everything you feel fades. It is not until fecal matter forms in your distal colon that you can again sense what is present and regain control of how it is moved.”

Much more than mere glue
The intestines fascinate the young researcher. In order to unlock their secrets, Scavuzzo concentrates on the glial cells which are ubiquitous in the intestinal tissue, alongside myocytes and neurons, and “about which we know so little.” Glia, translated literally from Greek, means “glue”. Since Rudolf Virchow first described them in the 19th century, they have been understood as mere mortar within the tissue. It is known today that glial cells are also involved in processes such as signal transduction, gut motility and immune defense.
Marissa Scavuzzo is based in Cleveland at the Institute for Glial Sciences, working with Paul Tesar, whom she refers to as “one of the leading global experts” in glia research. While her mentor focuses on glial cells in the brain, she specialized on glial cells in the digestive system. Her goal: to decipher the specific role of glial cells within the digestive process. To this end, it is crucial to no longer consider glia to be a uniform mass but rather “determine the individual functions of individual glial cells.” Only then will one be able to formulate specific statements about how glial cells change during the course of intestinal disease.

Biographical inspiration
This topic has been on the mind of the Texas native since childhood. Her mother suffers from a congenital shortened esophagus and had to endure multiple surgeries. As a result, family conversations frequently centered around digestion. Initially, this was one of the reasons Marissa wanted to become a doctor. Once in college, however, a new perspective opened up. Simply the thought of how many people she could potentially save through her own research motivated her. In addition, she loves the creative side of research: “Pondering something, following the wrong track, blazing new trails – it’s as exciting as a backpacking trip. I love both.”
Indeed, her research resembles a tour into the unknown. Initially, the postdoc had no tools with which to study the identity and functional variety of the cells. She had chosen difficult terrain: the enteric nervous system (ENS) (enteric refers to intestines) comprises a complex network of neurons and glia which is also known as the “second brain”. As such, it took an entire year until Scavuzzo had developed new cellular and molecular techniques that allowed her and her team to embark on their scientific quest.

Research in its infancy
Here, the researchers discovered a special subtype of intestinal glial cells which reside inside muscular layers and which she refers to as “enteric glia-hub cells.” She illustrates her “Science” article with a three-dimensional image of this specific cell type which, thanks to the insertion of a protein, glows green. Her photograph impresses how glia are interwoven with muscle and nerve cells. She was also able to show under the microscope that peristaltic movement is slowed when these glia-hub cells are removed from the murine intestinal muscular tissue. In reverse, this means that these glia-hub cells are indeed responsible for fine-tuning the wave-like movements of the intestines.
But how are these movements initiated? “In cooperation with muscle and nerve cells, they finely coordinate the rhythmic contractions without involvement of the brain”, says Scavuzzo. They function akin to a biosensor which registers the contents of the intestine and opens up in response to forces exerted on a cell membrane.
Marissa Scavuzzo is grateful for the Eppendorf award. She is hoping for more colleagues to enter this field which is still in its infancy. The development of pharmaceutical therapies for intestinal diseases has a long way to go – at least ten to twenty years. Until then, she will continue to map intestinal glia and start her own lab. This will most likely happen as early as the upcoming year.