Charting brain cell epigenomics to reveal origins of psychiatric disorders

In a revealing Genomic Press Interview published today in Genomic Psychiatry, Dr. Maria Margarita Behrens recounts an extraordinary scientific journey that wound through four countries and multiple disciplines before arriving at fundamental questions about how the brain develops and what goes wrong in psychiatric disorders. Her work now stands at the forefront of international efforts to decode the molecular signatures that define every cell type in the human brain.

Dr. Behrens serves as a faculty member in the Computational Neurobiology Laboratory at the Salk Institute for Biological Studies and holds an adjunct professorship in psychiatry at the University of California, San Diego. As a principal investigator in the National Institutes of Health BRAIN Initiative Cell Atlas Network, she contributes to generating comprehensive single-cell epigenomic atlases that researchers worldwide will use for decades to come.

A spark ignited on a psychiatry ward

The path to neuroscience was anything but direct. Born in Montevideo, Uruguay, and raised in Santiago, Chile, Dr. Behrens initially harbored ambitions of becoming an architect. The third of six daughters, she even enrolled in preparatory architecture school in Uruguay following the tragic death of her father in a car accident. Yet both parents had been scientists, and that intellectual heritage combined with an irrepressible curiosity eventually drew her toward biochemistry.

What transformed a biochemist into a brain researcher? The answer came through an unexpected encounter. Listening to patients in a psychiatry ward, Dr. Behrens found herself consumed by questions about the biological substrates of perception and reality. Why could these individuals not experience the world as others did? That question became a compass pointing toward decades of inquiry into the neural mechanisms underlying mental illness.

A transcontinental scientific education

Her training spanned continents in ways that seem almost deliberately circuitous. A master's thesis on aquatic fungi development at the University of São Paulo in Brazil. A doctoral dissertation on genetic networks governing sugar metabolism in yeast at the Autonoma University in Madrid. Postdoctoral work on the development of brine shrimp, also in Spain. None of these subjects appeared remotely connected to the brain.

Yet Dr. Behrens absorbed techniques and analytical frameworks during those years that would prove essential when she finally pivoted to neuroscience. This interview exemplifies the type of transformative scientific discourse found across the Genomic Press portfolio of open-access journals (https://genomicpress.kglmeridian.com/), where unconventional career trajectories often illuminate unexpected connections between fields.

Her transition came at Washington University School of Medicine in St. Louis, where she worked with Dr. Dennis Choi in the Department of Neurology. Six years of intensive study allowed her biochemistry and molecular biology background to merge with neuropharmacology. She learned which questions could be answered using neurons grown in culture and which required studying the brain as an intact organ.

The ketamine revelation

A pivotal observation emerged during her time studying brain aging at the University of California, San Diego. Effects of ketamine on the aging brain led to investigations that yielded surprising results. Phenomena observed in cultured neurons translated into unexpected mechanisms in living animals. The findings were published in Science and opened the door to the Salk Institute, first within the laboratory of Dr. Terrence Sejnowski and subsequently as an independent scientist.

Could ketamine's effects on inhibitory neurons explain some of its remarkable properties as a rapid-acting antidepressant? And what might this reveal about the fundamental organization of neural circuits? These questions connected her pharmacological observations to deeper mysteries about brain development.

Mapping every cell in the brain

A publication encountered while awaiting grant decisions redirected Dr. Behrens from ketamine pharmacology toward developmental epigenomics, initiating a long-standing and fruitful collaboration with Drs Joseph Ecker and Bing Ren. Today, her laboratory investigates how neural circuits form in the prefrontal cortex during the perinatal period and whether maternal environment can influence brain development through epigenomic modifications.

The work carries profound implications for understanding neurodevelopmental and neuropsychiatric disorders. When does the developmental program deviate from its intended trajectory? What molecular events during critical windows set the stage for conditions that may not manifest until adolescence or adulthood?

Through the BRAIN Initiative Cell Atlas Network, Dr. Behrens and collaborators have produced atlases of the mouse brain listing not only genes expressed in every cell type but also the regulatory regions governing that expression. A similar atlas of the human brain is now underway. These resources will enable researchers globally to target specific cell types with unprecedented precision, opening therapeutic possibilities that were previously unimaginable.

The collaborative imperative

Dr. Behrens articulates a philosophy of science that prioritizes teamwork over hierarchy. She describes her greatest talent as building collaborative teams where everyone contributes without regard to status. This orientation reflects a conviction that knowledge advances through collective effort rather than individual brilliance.

What cultural facets of the scientific community warrant transformation? Dr. Behrens points to funding structures and peer review systems that fail to reward genuine collaboration. The competitive pressures endemic to academic science, she suggests, impede the open exchange of ideas that produces breakthrough discoveries.

Her mentoring encompasses a remarkably diverse group: genomicists, behavioralists, computer scientists, and neuroscientists working together on problems that no single discipline could address alone. The model echoes the interdisciplinary ethos that Genomic Press champions through its commitment to advancing open-access medical research across traditional boundaries.

Beyond the laboratory

Outside professional life, Dr. Behrens treasures travel to national parks, music, and enriching conversations. She lists her favorite occupation as listening to music and painting. Her most treasured possessions are not material objects but relationships with family, friends, and colleagues.

When asked which living person she most admires, she names Svante Pääbo, the Nobel laureate recognized for his work on ancient DNA and Neanderthal genomics. And if she could dine with any historical figure? Charles Darwin, for his analytical thinking and the way he articulated his reasoning as he uncovered evolutionary principles.

Her life philosophy crystallizes in a motto both pragmatic and liberating: if you cannot do anything about it, call it good. For a scientist who navigated funding crises, geographic relocations, and disciplinary transformations, such equanimity appears hard-earned.

Dr. Maria Margarita Behrens's Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist's impact on the field, while also touching on broader human themes.