It’s Not the Structure, It’s the Context

Structural cell biology — also known as cryo-electron tomography, in situ cryo-EM and visual proteomics — has emerged as one of the most transformative approaches in modern biology. By imaging molecular machines directly within cells, the method offers something no other method can: structure in context. But what does context actually change?

In this Presidential Lecture, Alex de Marco will explore how technological advances in cryo-EM are expanding the reach of in situ structural biology, and why the resulting biological discoveries consistently challenge conclusions drawn from purified systems. Drawing on recent work conducted at the New York Structural Biology Center spanning chromatin organization, cytoskeletal self-assembly and membrane trafficking, he will argue that the most consequential variable in modern structural cell biology is not resolution but relevance. The structure of a molecule tells us what is possible. Its cellular context tells us what actually happens.

De Marco is the director of the Simons Electron Microscopy Center (SEMC) at the New York Structural Biology Center, leading the world’s largest cryo-EM facility with 15 transmission electron microscopes, three cryo-FIB/SEM systems and 46 staff serving nearly 1,000 active users. His research focuses on method development for cryo-electron tomography, correlative microscopy and sample preparation, with contributions including the PIE-scope, OpenFIBSEM, Square Electron Beam illumination, and nanocrate technology to overcome air-water interface artifacts. His work has appeared in Nature, Science and Cell. He holds adjunct appointments at Columbia University and Monash University. He also directs the NIH National Center for CryoEM Access and Training and the NIH National Center for In-Situ Tomographic Ultramicroscopy.