Center of Excellence for Structural Cell Biology provides the blueprints to the cell interior

Tinkerbella nana, a species of fairyfly not much bigger than the width of a human hair, found itself at the business end of an electron microscope. What the scientists at the other end saw was alien and beautiful — and deeply insightful. The images revealed that the fairyfly was, in fact, a microscopic swimmer, designed to row its bristly wings several hundred times a second to move through the relatively soupy air. 

Electron microscopy, in different forms, allows computer scientists to achieve semiconductor miniaturization on remarkable scales. It helped materials scientists understand why graphene — just one atom thick — is so exceptionally strong. In structural biology, the integration of cryogenic capabilities to maintain microscope temperatures below -197°C has revolutionized the study of proteins and large macromolecular assemblies — a revolution that continues to accelerate. 

With the establishment and rapid growth of the Cryo-Electron Microscopy and Tomography Center at St. Jude, cryo-electron microscopy (cryo-EM) has cemented itself as a core component of the institution. Cryo-electron tomography (cryo-ET), an emerging specialized application of cryo-EM, now offers researchers the chance to map these assemblies like never before: as they exist in cells. 

This pursuit is at the heart of the newly established Center of Excellence (CoE) for Structural Cell Biology at St. Jude. Through this CoE, the hospital aims to create the blueprints for next-generation structural biology in cells and tissues through the development and integration of multiscale imaging technologies. 

An established identity of innovation 

While this represents an ambitious advancement as part of the institution’s strategic plan, St. Jude researchers have consistently embraced new technology early to support fundamental biomolecular research. Since joining in 2017, Charalampos “Babis” Kalodimos, PhD, Department of Structural Biology chair, has harnessed emerging technologies to address key questions in human health through the establishment of multiple centers, including the Cryo-Electron Microscopy and Tomography Center. Scott Blanchard, PhD, Single-Molecule Imaging Center director, has leveraged his expertise in single-molecule imaging to assemble one of the world’s most comprehensive centers of its kind. In 2020, M. Madan Babu, PhD, FRS, Senior Vice President of Data Science, established the Center of Excellence for Data-Driven Discovery, ensuring the rapid expansion of data produced by St. Jude researchers is reliably transformed into actionable information for years to come. 

With the support of J. Paul Taylor, MD, PhD, Executive Vice President, Scientific Director, and Department of Cell & Molecular Biology chair, St. Jude is now poised to embrace another frontier in structural biology, as attention shifts to the cell interior. Like looking at the wings of a fairyfly to understand movement, researchers aim to see each component of the cell, from molecular machines to organelles, in incredible detail and in the context of everything that surrounds it. 

Skiniotis aims to observe proteins as they exist in the cell 

This new venture caught the attention of Georgios Skiniotis, PhD, CoE for Structural Cell Biology director. “What drew me to St. Jude was the sense that leadership was serious about building a cutting-edge imaging initiative — not just acquiring a capability, but actually pushing the field forward. There was a willingness to think ambitiously about integrating technologies across scales, from high-resolution molecular imaging to cellular and tissue-level visualization, and deploy these efforts to discover new biology,” Skiniotis said. “That ambition is infectious, and it creates an environment where people are encouraged to develop new approaches rather than simply apply existing ones.” 

Skiniotis’ lab, which he moved from Stanford University to St. Jude in 2024, has provided key insights into G protein-coupled receptors (GPCRs). These membrane-bound proteins translate signals from outside cells into responses inside and are the most common drug target for Food & Drug Administration (FDA)–approved therapeutics. He has been a member of the GPCR Collaborative since its inception in 2023. Led by Blanchard, the Collaborative also includes Babu, Jonathan Javitch, MD, PhD, of Columbia University, Robert Lefkowitz, MD, of Duke University and Alice Ting, PhD, of Stanford University. Most recently, Skiniotis used cryo-EM to present GPCRs as dynamic and multifaceted machines rather than static signal relays. 

His 2024 Nature study introduced a temporal element to cryo-EM to observe GPCR movement. This time-resolved approach demonstrated how subtle structural changes within GPCRs propagate to interpret a molecule binding event at one end and decode it into a signaling event at the other. Another Nature study, which Skiniotis published in 2025, showed that the strength at which molecules activate GPCRs can alter the speed at which signals are produced. The cryo-EM structures revealed that weaker activating molecules get the GPCR stuck in specific structural arrangements longer, thus slowing down signaling. 

Skiniotis is now looking to structural cell biology to continue this forward movement in GPCR functional studies. “These are membrane proteins with different forms and features; some have extracellular domains interacting with extracellular partners, while others have long domains inside the cell that influence function,” he explained. “We’ve never really been able to look at that space using purified samples; it’s very difficult. But through advanced tomography and complementary techniques, we may be able to capture these assemblies as they exist in the cell and derive high-resolution models from them.” 

Bringing structural biology into a new frontier 

The vision is clear: a center where researchers develop and refine new technologies in synergy with ample cryo-EM expertise and the infrastructure to plant St. Jude as a leader in the still-new field of structural cell biology. However, the approach is not just reserved for GPCRs. In fact, the CoE aims to deploy these extremely powerful technologies across the institution and develop a pipeline to bring similar insights to every corner of the cell. The Department of Cell & Molecular Biology and the Department of Host-Microbe Interactions have become early partners in the effort, each agreeing to support CoE faculty members along with the Department of Structural Biology. 

“Regardless of the process they study, all researchers want a high-resolution model of the cell — both spatially and temporally — and to understand how it operates. Based on these high-resolution pictures, we want to model components, run predictions and understand how it all works,” Skiniotis explained. “Our goal is to move away from the test tube, which allows for controlled study but cannot recapitulate physiology, and look at these systems in context, to look at biology as a multicomponent system.” 

As Skiniotis lays the foundation for this pursuit, one thing is clear. The CoE for Structural Cell Biology is not just a bourgeoning resource to probe fundamental questions of cellular function. It is also a signal to the wider community that St. Jude is ready to be at the forefront of another wave of discovery.