Finding the Funny: A Conversation with Paola Arlotta, 2023 FASEB Excellence in Science Mid-Career Award Recipient

10/22/2024

 By Sarah Petrosky

Paola Arlotta, Golub Professor of Stem Cell and Regenerative Biology at Harvard University, was the recipient of the 2023 FASEB Excellence in Science Mid-Career Award for her significant contributions to the field of neurobiology and for her contributions to the scientific community as a mentor and leader. She will deliver her award talk at the 2024 Society for Developmental Biology Meeting in Atlanta, GA.

A deeply curious person who is attracted to the beauty found in the natural world, Arlotta is motivated by the feeling she gets when she discovers something new and unexpected, something she describes as “finding the funny.”

Arlotta’s curiosity was encouraged early in her life by her high school science teacher, Professor Vecchia. Through Vecchia’s hands-on experiments and accessible language, Arlotta learned to see science as “a journey, rather than difficult material to digest.” Once in university, she was immediately drawn to developmental biology, despite the lack of developmental biology courses available to her in the curriculum. The little bits of embryology and development that were scattered throughout the rest of her classes attracted her with their elegance and complexity.

“I wish I had any inclination to be able to turn what we see in the lab under the microscope into art that others could see, because there is such amazing beauty,” she said. When she began her post-doctoral training at Harvard University, she made the decision to specialize in neurobiology after seeing a piece of the cerebral cortex under the microscope, which she described as seeing a whole other world.

When Arlotta launched her lab, the field of neurobiology understood development of neurons to flow in only one direction—from undifferentiated to differentiated—with cellular identity becoming unchangeable once neurons have differentiated. The established model was that new neurons are not made, and existing ones are neither recycled nor renewed. Counter to this established hypothesis, Arlotta’s lab found that neurons were capable of being reprogrammed from within the brain.

Arlotta and her postdoc Caroline Rouaux were able to reprogram one type of mouse neuron, callosal projection neuron, into another, corticofugal projection neuron. The reprogrammed cells acquired the molecular characteristics of their new cell type and changed their axonal connectivity to mirror the behavior of corticofugal projection neurons. She remembers the moment when Rouaux pulled her to the microscope to show her some slides of brain slices, where markers that should have been in the deep layers were also present in the upper layers. Both scientists immediately knew they had found a challenge to the established dogma that neural cells cannot change identity late in development.

Arlotta has learned to see counterintuitive data as a success. The data that look funny at first can sometimes be the best moments of a project. Without the funny, without the unexpected, science becomes boring, and the strict adherence to dogmas becomes limiting. Arlotta encourages students to persist through the disappointment that they sometimes feel when faced with funny data.

“You’re going to have a lot of feelings at that moment. You should go for a walk, or go do something with your friends. Put it in the drawer today, and tomorrow we take it out again with a fresh mind.”

She emphasizes that it’s important to frame unsuccessful experiments not as failures, but as part of the path to discover the correct answer.

Arlotta continued to “find the funny” when her lab investigated myelination in neurons. Myelin is an insulating tissue that wraps around the axons of neurons. Her lab observed that the most advanced neurons in the nervous system have less myelin. It took them some time to move away from the mindset that new neurons only needed time to develop myelination, rather than the neurons themselves employing different strategies in the neural network. In fact, leaving an axon unmyelinated may be advantageous, as it facilitates branching out to connect with other neurons.

Arlotta’s lab has recently focused on growing brain organoids, producing a single-cell atlas of human brain organoid development. With the epigenetic, transcriptomic, and spatial data collected in this atlas, the lab identified genes predicted to have important roles in human neural cell diversification and described the transcriptional activity of early human callosal neurons. Arlotta was always fascinated by how life puts itself together in a self-organized way without knowing what self-organization is, and now she has organoids that are ideal for investigating the fundamental mechanisms underlying brain development. She also sees potential uses for these organoids in understanding neurological diseases.

As a first-generation college student, Arlotta finds the presence of role models necessary to encourage young scholars and scientists, and anyone who encourages creativity and discovery can be a successful role model. “You don’t have to be educated to be curious,” she said. Without the encouragement of her family, she might not have pursued a career in science. She remembered telling her father that she wanted to attend a vocational high school, which would teach her the skills to get a job, and her father told her in response that she had three choices: college prep for the sciences, college prep for the humanities, or college prep for the arts. She resisted her father’s advice at the time, but in retrospect is thankful that he encouraged her to reach for higher education.

Arlotta takes her responsibilities as a mentor seriously. She said the best thing she can do is to inspire her students with the excitement of discovery that is inherent to science. She also tries to consider the background of her students in her mentoring strategies, and recognizes that lack of confidence can be more prominent in women scientists. She is especially proud of the number of women she has trained.

Regarding graduate students, Arlotta emphasizes they should be failing, because we’ve all failed. Every failed experiment is just “water under the bridge.” She finds that graduate students require encouragement to make it through this period of failure.

For postdocs, Arlotta focuses on figuring out who they are, and encouraging them to take the path that will bring them the most fulfillment. Silvia Velasco, one of Arlotta’s former postdoctoral trainees currently running her own lab at Murdoch Children’s Research Institute in Australia, wrote that Arlotta’s mentorship began long before Velasco worked in Arlotta’s lab. As an early career scientist, Velasco attended a guest lecture given by Arlotta at the National Hospital for Paraplegics in Toledo, Spain. Arlotta graciously met with Velasco that day and continued to offer her support and encouragement for many years before Velasco joined her lab in 2017.

As a successful academic, Arlotta is thankful for the support she’s received herself. She said, “I am very grateful to my colleagues, to this community I’m privileged to be a part of—the global community of scientists, of people who are willing to travel the world, meet at conferences, spend time with each other, challenge each other’s ideas, recognize each other’s successes. Nobody does this alone. We are the product of the people around us from the past, the present and the future.”

Last Updated 10/22/2024