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Molecular film creator – Scope

my last story for Stanford Medicine magazine focused on what is called cryogenic electron microscopy. Expect! Do not go. It’s interesting, I promise.

Think wavy bits of SARS-CoV-2, scientists tweaking LSD to change its impact on the brain and discovering how to end HIV once and for all. Behind a myriad of drugs, nuanced details about disease manifestation, and so many other aspects of understanding biology, lies an effort to piece together a picture—sometimes a movie—of how molecules look and function. . This allows scientists to uncover all the secrets molecules hold, how they work to perform tasks in the body, and how these operations can falter during illness.

In this story, imaging is a shining beacon of knowledge, and scientists are increasingly turning to a burgeoning technique, called cryo-EM, to decipher biology. This technique compiles thousands of different images of the same molecule, distorted and frozen in various shapes, to build a holistic picture of its structure.

Changes in the structure of a molecule often underlie its actions. But even the clearest picture doesn’t capture the dynamic nature of molecules, which are key to understanding what proteins do and how they do it. This is where cryo-EM comes in: it has the ability to detect and track proteins as they would move in nature.

If you were an alien…

Cryo-EM expert Georgios Skiniotis, PhD, professor of molecular and cellular physiology and structural biology at Stanford Medicine, puts it another way: imagine you are an alien visiting Earth for the first time. Your mission: Capture the complexities of human movement through photographic evidence and return home. What could you shoot? Maybe a photo would show someone standing; another, someone seated; and another, someone halfway.

The static images give an idea of ​​what a person looks like – four lanky appendages with some kind of knob that sits on top – all in different conformations. But movements between these poses are lost, as is information about function and how that person interacts with their environment. If you really want to know how humans move from position to position, you need something more sophisticated, with thousands of closely related photos; something more like a movie. This is what cryo-EM offers.

With a movie, you can see how one state transitions into another — a premise that Wah ChiuPhD, Professor of Microbiology and Immunology and Bioengineering, and Christopher BarnesPhD, assistant professor of biology, is capitalizing on understanding how viruses, such as SARS-CoV-2 and HIV, infect cells and how to stop them.

See how these scientists are harnessing this powerful imaging technique to uncover the secrets of molecular variety to develop treatments and vaccines, and find out what makes a molecule work.

Photo by Timothy Archibald