For Alisha Jones, the journey into biophysics began not in a university lecture hall, but in a high school laboratory in Toledo, Ohio. As a junior in high school, she was selected to participate in the American Chemical Society’s Project SEED Program. Jones spent a transformative summer in Ronald Viola’s lab at the University of Toledo, learning the fundamentals of biochemistry. Looking back at slides from her first lab presentation, she finds them “hilarious, to say the least,” but they document a passionate, ambitious 16-year-old studying aspartate semialdehyde dehydrogenase (ASADH) as a potential target for antimicrobial development.
“I aimed to determine their structures by x-ray crystallography to facilitate structure-based drug design,” Jones recalls of her initial plan to work with ASADH from six different species. She managed to generate plasmids for all six species, successfully expressing and purifying only one protein, but the experience was formative. “That was a really cool summer—I returned the following year to tackle a different project and have been doing research ever since,” she shares.
Born in New Haven, Connecticut, Jones moved with her family to Toledo around age 10, where she remained until leaving for college. Neither of her parents worked in science—her mother was a nurse and her father a construction worker—but they recognized early signs of scientific curiosity. “I think my parents always had a hunch that I was going to be a scientist,” Jones remembers. “I mixed a lot of things together in their bathroom.”
Jones pursued her undergraduate education at Miami University, earning her bachelor’s degree in chemistry and zoology before heading to the University of Washington for her PhD in chemistry. It was during graduate school that she found her true calling in RNA structural biology, drawn by two specific interests: learning nuclear magnetic resonance (NMR) spectroscopy and developing drugs for human immunodeficiency virus (HIV). Gabriele Varani’s lab at the University of Washington offered the perfect intersection of both. “The lab that I joined used NMR to determine structures of RNA to facilitate the structure-based design of peptides that could bind those RNAs with high affinity,” she provides.
Her first doctoral project focused on designing peptides that could bind to the HIV transactivation response element, to block its interaction with the HIV trans-activator protein. “Blocking this interaction prevented transcription of the viral RNA,” Jones explains. “This project highlighted the importance of RNA structure.”
Jones’s subsequent work on long noncoding RNAs (lncRNAs) revealed fascinating insights about evolutionary conservation. She discovered that the Cyrano lncRNA, crucial for embryonic development, adopts a structure that is conserved across species as evolutionarily distant as zebrafish and humans; remarkably, this structural conservation was maintained despite the RNA lacking sequence conservation. Although she found the project engaging, it also exposed significant limitations in existing methodologies. She notes, “Their large sizes complicate NMR spectroscopy. Their dynamic nature makes x-ray crystallography a nightmare.” This realization sparked a pivotal decision: going forward, she would focus on studying large RNAs and on developing biochemical and biophysical methods to make it easier to investigate them.
As a postdoctoral researcher, Jones demonstrated the critical role of RNA structures across diverse cellular processes, including T cell activation, microRNA processing, X-chromosome inactivation, and viral replication. These findings reinforced her conviction that understanding RNA structure is fundamental to understanding cellular function.
Today, Jones serves as Assistant Professor of Chemistry and holds the James Weldon Johnson Assistant Professor Chair at New York University. Her laboratory focuses on developing and applying methods to investigate how RNAs transition between different structured states. “This is important because it establishes a fundamental model for how RNAs function but also broadens the structures one can therapeutically target when an RNA is implicated in a disease,” she explains. The work sits at the intersection of RNA structural biology, biophysical chemistry, and chemical biology—fields that demand both technical precision and creative problem-solving.
When asked about the biggest challenge in her career, Jones mentions something many people struggle with: responding to emails in a timely manner. “I am still working on that,” she admits. “If you’ve emailed me and I haven’t responded to you, I promise, it is me, not you. ChatGPT told me that one way to tackle this is to set a specific time in the day to answer the emails. Someone else told me to answer the emails that are super easy right away and save the emails that take time for later. I am still facing this. If you have ideas, let me know. Otherwise, email me again.”
What captivates Jones most about biophysics is its foundation in audacious thinking. “I think the approaches we use come from crazy ideas that on paper must work, and we somehow find a way to make it work in the end,” she says. The most rewarding moments in her work come from those spontaneous breakthroughs: “I really enjoy going into the lab with a ‘4 AM thought,’ expanding on it in my notebook, giving it a go, and finding that it works!”
Those “4 AM ideas” often draw inspiration from unexpected sources, which is one reason Jones values the Biophysical Society and its Annual Meeting. “It’s sometimes helpful to be in an environment outside the lab to hear about new methods or approaches,” she reflects. “I like to cast a wide net for inspiration. You never know where your next 4 AM idea will come from.”
Looking toward the future, Jones’s plans involve translating ideas and approaches common in protein research and applying them to RNA. Her ultimate goal is to develop a new method that makes it easier to study the conformational dynamics of RNA, regardless of its size.
Outside the laboratory, Jones maintains diverse interests that reveal a creative spirit extending beyond science. She’s an avid reader of science fiction and fantasy, enjoys building Lego sets, and likes wandering a city or hiking in nature. She also likes going dancing with friends, cycling long distances, and thrifting for vintage 90s clothing. If circumstances had led her down a different path, she imagines she might have become an architect or a writer—professions that, like science, value both creativity and precision.
For young scientists entering the field, Jones offers advice rooted in her own experience. “I think biophysics is driven by creativity,” she says. “That crazy idea that you have—give it a try! Use your colleagues and advisors to help refine your idea. It could be the next big thing.” Bold ideas, persistent curiosity, and collaborative refinement can transform even the most audacious 4 AM thoughts into meaningful scientific contributions.