Student of sleep: A profile of Lizzie Tilden

In the early-morning, sub-zero temperatures of a Boston winter, what Lizzie Tilden would have loved more than anything was to stay in bed – at least until the sun came up. Instead, she dragged herself from her dorm room, trekked across the snowy Brandeis University campus, pressed a power button for 5 seconds to avoid losing all the data she had collected in the previous 240 hours, then headed back to bed. She knew there had to be a better solution to these all-too-frequent system failures.

When Tilden first joined the lab of Gina Turrigiano, PhD, the Joseph Levitan Professor of Vision Science at Brandeis University, as an undergraduate student, she didn’t expect to find herself knee-deep in programming to engineer her way out of unpredictable lab emergencies. A dual biology and anthropology major with plans to attend medical school like her parents did, Tilden joined a team with then-postdoc Keith Hengen, PhD and then-grad student Alejandro Torrado Pacheco in pioneering large-scale, in vivo electrophysiological recordings that lasted 10 days – and sometimes required late-night trips back to the lab to reboot the amplifier system. Fed up, Tilden programmed a robotic finger to reset her equipment for her when it failed, even if she was fast asleep. “I unlocked this whole different part of my brain that I didn’t really know that I had,” she says.

Overcoming the experimental challenges she faced, Tilden was able to use these large datasets to investigate why light-sensitive neurons in the visual cortex do not seem to change their firing rates between light and dark conditions, which ultimately resulted in her first peer-reviewed publication. With Hengen and Torrado Pacheco’s mentorship, Tilden learned to “think like a researcher,” she says, and she came to realize that she would not be ready to give up science when the time came to pursue medicine. Hengen, now an assistant professor of biology at Washington University, offered a five-letter solution to this problem: MD/PhD.

A grant-writing, collaboration-forging technician

In 2017, as Tilden was entering her senior year of college, Hengen left Brandeis to join the faculty at Washington University. One of his first moves as he unpacked his lab was to offer Tilden a job as a research technician. She was “the rare student who right off the starting line checks all the boxes,” Hengen says, to “create that wavelength and that culture that I personally believe is probably the most important element of any lab in determining its trajectory and scientific impact and how fun it is to show up at work.”  

I wanted to see if there was something that I never had thought of that really caught my attention.

Lizzie Tilden

“He really planted the seed in my head that WashU was a cool place to be,” Tilden says, prompting her to consider life in the Midwest and ultimately make the move. Despite her initial apprehensions about leaving her “northeastern bubble,” Tilden says, she has found her niche in St. Louis, as she has established herself as an active member of the university and broader St. Louis communities. She cuddles babies twice a month as a volunteer in the neonatal ICU and plays competitively and coaches an ultimate frisbee team at a high school in St. Louis County. “There is plenty to do and see, and there are so many community events to take advantage of.”

In Hengen’s lab, Tilden “built this future-focused vision and turned that into a workable reality,” Hengen says, this time with an initiative to start a new line of scientific inquiry. Within weeks of starting in the lab, Tilden began an independent research project, collaborating with David Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology at Washington University School of Medicine, to explore the relationship between Alzheimer’s disease and sleep/wake states. Tilden composed and received a 2019 Knight ADRC Pilot Award – an internal Washington University grant that funds research on aging and dementia.

“My prognostication about [Tilden’s] contributions to the lab and my research were spot on,” says Hengen. Her influence remains at the forefront of the Hengen lab, as previous lab members Clayton Farris and Sahara Ensley carried out her plan to record hippocampal dynamics over the entire lifespan of an animal. This effort has yielded a Netflix-sized dataset that Hengen plans to use as the basis of an R01 grant. From these data, his team hopes to reliably predict which animals will develop neurodegenerative disease, prior to the onset of the molecular pathology currently used to characterize disease states, Hengen explains. Tilden may just have generated “the world’s best biomarker.”

Through these experiences collaborating across campuses, Tilden immersed herself in the neuroscience community at Washington University. “This place is super special,” she says. While penning the Knight ADRC grant, Tilden simultaneously submitted her applications to MD/PhD programs across the country but decided to stay put at WashU and enroll in the medical scientist training program (MSTP).

Deep into sleep

By the time Tilden began research rotations for her MD/PhD program in the summer of 2020, she had already decided that it was time to expand her network and break out of her comfort zone. “I wanted to see if there was something that I never had thought of that really caught my attention,” she says.

Although they had met previously, when Tilden attended a “rotation talk” by Yao Chen, PhD, assistant professor in the Department of Neuroscience at the school of medicine, as a new MSTP student, she was immediately struck by Chen’s innovative use of a relatively new optical imaging technique to study how signals are integrated and modulated among populations of cells in the brain. Tilden and Chen both felt that their complementary approaches to studying the brain could help them construct a bridge between Tilden’s systems/computational and Chen’s molecular/cellular neuroscience backgrounds, to ultimately yield a more complete understanding of how the spatial and temporal features of molecular signals inside the cell generate meaningful behavioral outputs through modifications of cells and circuits.

My prognostication about [Tilden’s] contributions to the lab and my research were spot on.

Keith Hengen, PhD

Since rotating in and joining the Chen lab during the COVID-19 pandemic, Tilden has established herself as an integral part of the group: a problem-solver and “real collaborator,” says Chen. The two have worked together to build a new fluorescence lifetime photometry rig, which allows researchers to analyze many biological signals beyond calcium in freely moving mice. Chen has overheard Tilden and fellow graduate student Pingchuan Ma slapping high five and shouting “teamwork!” when they accomplish something.

True to form, Tilden has been an innovator, stepping away from the “bread and butter” projects of the group, as Chen puts it, to pioneer sleep research in the lab. Tilden is currently working to combine the Chen lab’s ability to monitor many biological signals over long periods of time in freely moving animals with her expertise in monitoring sleep/wake states and computational analysis. By doing so, she hopes to generate hypotheses about how sleep serves its beneficial functions to immune health or learning and memory at the macroscale. To drive this project forward, Tilden and Chen have instituted a weekly two-person journal club to better understand the nuances of sleep research and to develop their experimental plan.

Tilden says she is eager to see how her sleep project in the Chen lab unfolds from its current nascent stage. “I’m just excited to see where the data take me.”