Marissa Scavuzzo is the winner of the 2023 Eppendorf & Science Prize for Neurobiology for research revealing how specialized glial cells, operating independently of the brain, are embedded within the walls of the gut and fine-tune intestinal function.
Scavuzzo's prize-winning work provides new insights into the diverse functions of different enteric glial cell subtypes and their role in gut health and gastrointestinal disease.
The annual Eppendorf & Science Prize for Neurobiology recognizes the important role of neurobiology in advancing the understanding of the functioning of the brain and nervous system. The winner receives $25,000 and publication of their essay in the November 3 issue of Science.
"I am fascinated by digestion; it is an incredibly ordinary and extraordinary process," said Scavuzzo, a HHMI Hanna H. Grey Fellow at the Case Western Reserve University School of Medicine. "Just thinking about all of the different cell types interacting and moving around together like a meticulously orchestrated ballet keeps me up at night."
Scavuzzo also has a personal interest in the topic — her mother has had lifelong gastrointestinal dysfunction — and she hopes that her work in this space will continue to reveal insights that could help bring new therapies to patients like her mother in the future.
The enteric nervous system (ENS) — a complex network of neurons and glia often referred to as the "second brain" — controls our ability to move food through the gastrointestinal tract and operates independently of the central nervous system.
"We all know that the brain is very complex," said Scavuzzo. "But the gut rivals the brain in its complexity and independence."
It takes conscious effort to swallow a bit of food or a drink of water. However, after it moves into the esophagus down the throat, peristalsis — an involuntary wave-like movement of the muscles in the gastrointestinal tract — takes over.
"Digestion is required for survival, and for it to occur, dozens of different cell types in the gut must come together to sense what is there, decide what to do with it, and move it all in one direction," said Scavuzzo.
The ENS innervates the entire gut — from the esophagus to the rectum — and intertwines each layer of the gut, where there is an opportunity for glial cells to interact with many other types of cells.
Although this "brain inside your gut" plays a crucial role in survival, the identities and functional diversity of the cells that comprise this system remain poorly understood.
To address this, Scavuzzo and her lab developed new cellular and molecular technologies that enabled researchers to define enteric glial diversity at the molecular, morphological and tissue level, which revealed a specific subpopulation of enteric glia found exclusively in the muscle layer of the gut, which the researchers named enteric glial hub cells.
By mapping the connectome, or the "wiring diagram" revealing how these cells are connected to others, Scavuzzo and her colleagues discovered that these distinct cells act as a type of biosensor and directly sense gut contents through PIEZO2, an ion channel that opens upon application of force to a cellular membrane.
According to Scavuzzo's work, enteric glial hub cells respond to this force to orchestrate and fine-tune the function of enteric neurons and other cells that coordinate the muscle contractions that drive peristalsis and move material through the gastrointestinal tract.
"Knowing what enteric glial subtypes do and how they respond to stimuli is essential to fully understand digestive processes," said Scavuzzo.
Scavuzzo noted that these hub cells are just one of many enteric glial subtypes, and a growing body of research has shown that enteric glia, as a whole, contribute to many digestive processes.
"This mechanistic insight into how enteric glia contribute to intestinal physiology and dysfunction will pave the way towards therapies for the millions of GI [gastrointestinal] and neurodiverse patients suffering from gut disturbances," said Scavuzzo.
To Scavuzzo, winning the Eppendorf & Science Prize for Neurobiology is a tremendous honor and helps bring attention to this small but powerful field of research and inspires others to work in this area.
"Eppendorf and the journal Science have awarded this prestigious prize for over 20 years. Many awardees have gone on to become leading scientists in their field," said Axel Jahns, Ph.D., vice president of corporate citizenship and governmental affairs at Eppendorf SE. "Congratulations to Marissa Scavuzzo on her amazing achievement in winning this year's award."
Mattia Aime for his essay "To 'feel' better, sleep on it: Emotional memories are consolidated during REM sleep." Aime received his undergraduate degree in neurobiology from the University of Pavia and a Ph.D. in neuroscience at the University of Bordeaux. Currently completing a postdoctoral fellowship at the University of Bern, Aime's research is focused on the mechanisms behind emotional memory consolidation during sleep, with the goal of identifying potential new therapeutic targets for treating affective disorders, such as PTSD and anxiety.
Michael Skinnider for his essay "From single cells to neural circuits: mapping neural circuits in high-throughput with single-cell genomics." Skinnider received his undergraduate degree from McMaster University and a M.D./Ph.D. from the University of British Columbia, during which he was also a visiting Ph.D. student at the École Polytechnique Fédérale de Lausanne. At his laboratory in the Lewis-Sigler Institute for Integrative Genomics and the Ludwig Institute for Cancer Research at Princeton University, Skinnider's research focuses on the application of machine learning to problems in biology, chemistry and medicine.