Molecular movie maker – Scope

My latest story for Stanford Medicine magazine focused on something called cryogenic electron microscopy. Wait! Not leave. It’s interesting, I swear.

Think shards of SARS-CoV-2, scientists tampering with LSD to change how it affects the brain and figure out how to get rid of HIV once and for all. Behind a myriad of drugs, nuanced details of disease manifestation, and so many other aspects of understanding biology, there is an effort to put together a picture – sometimes a film – of how molecules look and function. This allows scientists to learn all the secrets of molecules, how they operate to perform tasks in the body, and how those operations can falter during illness.

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

Changes in the structure of a molecule often underlie its actions. But an image, even the clearest, does not 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 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: to capture the intricacies of human movement through photographic evidence and return home. What could you shoot? Perhaps a photo would show someone standing; another, someone sitting; and another, someone in the middle of the step.

The static images give an idea of ​​what a person is like – four lanky appendages with a kind of knob at the top – all with different conformations. But the movements between those poses are lost, as is information about function and how that person interacts with his or her environment. If you really want to know how humans flow from one location to another, you need something more sophisticated, with thousands of closely related photos; something more like the movie. This is what cryo-EM offers.

With a film, you can see how one state transitions to another – a premise that Wah Chiu, PhD, professor of microbiology, immunology, and bioengineering, and Christopher Barnes, PhD, assistant professor of biology, are capitalizing to understand how viruses, how SARS-CoV-2 and HIV infect cells and how to stop them.

Learn more about how these scientists are harnessing this powerful imaging technique to unearth the secrets of molecular variety to develop treatments and vaccines and find out what makes a molecule work.

Photo by Timothy Archibald

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