In one sense, Marcella Birtele is following in her father’s footsteps: he works as an electrician in Italy, and she studies the electrophysiology of the brain as a postdoctoral fellow in Giorgia Quadrato’s lab at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.
“When I have doubts about resistance or problems with electricity for my experiments, I talk with [my dad] and get input about that. The basic principles are similar,” said Birtele, who was recently awarded a Choi Family Postdoctoral Fellowship, which provides support to recruit exceptional postdoctoral fellows to USC Stem Cell laboratories.
In another sense, she is venturing into uncharted territory as the first person in her family who earned a PhD. The granddaughter of farmers, Birtele grew up in the small town of Grezzana in an agricultural area of Italy, best known for its wine and Prosecco.
During a fifth-grade science project, she began reading about how the central nervous system orchestrates both autonomous responses such as digesting food, as well as more intentional actions such as walking across a room.
Her fascination with the nervous system inspired her to pursue a bachelor’s degree in biology from the University of Ferrara and a master’s degree in neuroscience from the University of Trieste.
At the same time as she was pursuing these studies, both of her grandmothers were diagnosed with neurological diseases: one with a rare autoimmune encephalitis, and the other with Parkinson’s disease, a neurodegenerative brain disorder that starts with a tremor and often leads to declines in movement, memory and mood.
With a renewed commitment to pursue research that could make a difference for patients, Birtele moved to Sweden to work in the laboratory of Malin Parmar at Lund University. Parmar’s group is using stem cells to generate the specific type of cell lost in Parkinson’s disease: neurons that produce the neurotransmitter dopamine.
“Sweden is very different from Italy,” said Birtele. “It was challenging, but the fact that I was doing what I love to do in an engaging work environment was the only reason I was able to stay in dark and cold Sweden for years.”
In the Parmar laboratory, Birtele measured the electrical activity of stem cell-derived dopamine neurons, and found it equivalent to that of the dopamine neurons naturally present in healthy brains. These stem cell-derived neurons are now approved for implantation into patients’ brains as part of a clinical trial to treat Parkinson’s disease.
“For me, it’s always about why people develop these diseases, and what are the mechanisms,” said Birtele. “So it’s about trying to help them but behind the scenes, and trying to understand what’s happening and if there is a way to treat these diseases.”
Near the end of her PhD studies, she began to generate rudimentary brain-like structures, called organoids, as a way to grow better dopamine neurons. As she watched the organoids developing in the laboratory, she became increasingly intrigued by how this process can go awry in an embryo and lead to neurodevelopmental disorders.
“For me, this work is even more important, because you can see the effect that you might have on the life of these small children,” she said. “So if you really understand what’s going on, and if you hopefully find a way to treat these problems, you could actually change the future of many people that still have years and years in front [of them] to live.”
She decided to shift her focus from neurodegenerative diseases to neurodevelopmental disorders, and moved to Los Angeles to become the Choi Family Postdoctoral Fellow in the laboratory of Giorgia Quadrato, who is an assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at USC. At the time of her arrival in November 2020, Los Angeles was in the throes of a terrible surge of the novel coronavirus. Due to pandemic delays, it took nearly five months for Birtele to receive a social security number, which prevented her from getting a driver’s license or opening a bank account. She was barred from traveling to visit her family in Italy, and her boyfriend had to postpone his move from Sweden to the U.S. due to a delay in visa processing.
“With the pandemic, every single thing was difficult,” she said. “But during the last few months, I’m seeing the positive things about Los Angeles—for sure, the weather after being in the dark and cold. And I’m starting to appreciate all the different things you can do. You can go hiking, or you can go to the mountains or to the ocean. And I’m actually loving the vibes of the city right now.”
Birtele is also enjoying her time in the laboratory, where she’s using patient cells to generate brain organoids with a mutation in a gene called SYNGAP1, which can cause intellectual disability, epilepsy and autism spectrum disorders. By studying these organoids, Birtele hopes to reveal precisely how this mutation impacts neural circuitry, electrophysiology and functionality.
“I feel so lucky that such a remarkable and talented postdoctoral fellow decided to join our lab,” said Quadrato. “I truly think that Marcella is poised to make important discoveries, and her unique expertise is already benefiting several projects in my lab. The Choi Fellowship will assist Marcella in pursuing her goals and in becoming very competitive in this field.”
Birtele added, “I’d like to thank the Choi Family for their support.”
In the future, Birtele aspires to run her own laboratory as a principal investigator at a university, and she considers Quadrato an ideal mentor.
“It’s great to see her in action, and she’s a brilliant scientist,” said Birtele. “She’s also a woman in science, and it’s good to have that vision right now and to get input on how to be a principal investigator as a female. And being Italian, she can understand when I say I miss my family! So I see her as a role model, since in the future, I would like to be in academia.”