Harvard Junior Fellow William Allen and Professor Xiaowei Zhuang of the Department of Chemistry and Chemical Biology have been chosen as winners of the 2020 Star-Friedman Challenge, which provides funding to Harvard researchers engaged in high-risk, high-impact research across a variety of fields. Allen, in collaboration with Zhuang, will use the Star-Friedman challenge funding to pursue a project called “Imaging the cellular and molecular basis of brain aging.”
Allen is also the first author of a paper published in Nature Human Behaviour on August 26. The paper discusses findings from the How We Feel Project, an initiative that collects self-reported data on COVID-19 symptoms through an app. Based on analysis of 500,000 self-reports made through the app, the HWF team was able to identify several occupational and demographic risk factors for COVID-19, gather data on presymptomatic individuals, and track how participants are responding to social distancing, according to the paper. Allen has been analyzing data for HWF as a side project through his collaboration with Feng Zhang’s lab at the Broad. With Harvard’s labs reopening, Allen will be focusing on his neuroscience projects.
Allen is one of two Harvard Junior Fellows in the MCB department. Sponsored by the Harvard Society of Fellows, a Harvard Junior Fellowship is a prestigious appointment that enables early-career researchers from all disciplines to conduct research at Harvard. It differs from a postdoctoral position in that Junior Fellows have PI rights when applying for grants. Allen is working with both Zhuang’s lab in the Department of Chemistry and Chemical Biology and the Dulac Lab in MCB on tools for addressing elusive questions in neurobiology.
“Will Allen came to Harvard with already a long list of spectacular achievements as a graduate student with Karl Deisseroth and Liqun Luo at Stanford,” says MCB faculty Catherine Dulac. “He has now many interesting and creative ideas on how to exploit and further develop the most powerful approaches of microscopy and neuroscience to address fundamental and so far intractable questions on the organization and function of behavior circuits. I am looking forward to seeing how these projects develop in the next few years!”
Allen is a relative latecomer to biology. Growing up in Berkeley, California, he wasn’t especially interested in the life sciences. He entered undergrad at Brown University intending to become a history major. However, participating in iGEM, an international competition that encourages undergraduates to work on synthetic biology projects, changed his mind. “I liked the idea that you could build things with DNA and engineer little genes into animals,” he recalls.
After graduating from Brown in 2012, he spent a year studying computational biology and neuroscience at University of Cambridge. Working in Gregory Jefferis’s lab at the MRC Laboratory of Molecular Biology, he learned about olfaction in Drosophila and grew to appreciate how biology can hinge on “granular” molecular details.
Allen’s current neuroscience research at Harvard traces back to his graduate work at Stanford. One of the projects that garnered researchers’ attention was STARmap, an RNA-sequencing technology that can provide single cell transcriptomes from many cells across an intact piece of tissue.
He also developed and applied a technique for simultaneously recording activity in thousands of neurons across the brain. Crucially, the technique captured spatial data, allowing Allen and his colleagues to create high resolution maps of where the neural activity occurred.
“I found that actually this very small population of a few hundred neurons that are dedicated to thirst widely broadcast their activity throughout the brain and coordinate this brainwide state,” Allen says. Rather than being clustered together in one “thirst center,” these thirst-sensitive neurons were distributed throughout the brain—an insight that led to publications in several major journals.
Though he develops tools, Allen is primarily interested in understanding biological and cognitive pathways. “I’ve gotten more interested in—rather than trying to understand how particular behaviors are implemented—the fundamental properties of neurons and the brain and how those are shaped by the animal’s environment,” he says. His Star-Friedman Challenge project ties into his interest in how these properties of neurons change over time.
Allen thinks about his approach to neuroscience in terms of layers. “Right now, there’s sort of a separation between circuit systems neuroscience, where people mostly focus on behavior and activity within individual neurons and how they’re wired together into circuits,” he says. “Then there’s molecular, cellular, developmental neuroscience, where people study specific axons, molecules, or cell types, or ion channels.”
Historically, most neuroscience studies have focused on variables within just one of those realms, but the challenge for 21st century neuroscientists is understanding how the different layers—the genetic, the proteomic, the synaptic, the connectomic, the physiological, and the behavioral—all shape each other. Allen’s goal is to develop technologies that will enable researchers to collect data on multiple levels simultaneously across wide swaths of the brain, first at Harvard and eventually in his own lab.
“There’s kind of a conceptual gap between those two levels, where the people who study genes aren’t fully integrated with the people who study neurocircuits or behavior,” he adds. “I’d like to bridge that gap in some way.”