Shengjie Feng channels the powers of cryogenic electron microscopy

Shengjie Feng, Ph.D., headshot

New Sanford Burnham Prebys researcher seeks to illuminate the hidden recesses and secrets of cellular and molecular biology

Cryogenic electron microscopy (cryo-EM) is science’s view of the future, or more precisely, a look at life at the smallest of scales. The imaging technology uses the very tiny wavelengths of electrons (much shorter than the wavelengths of light) to make clear images of equally tiny things.

With cryo-EM, researchers can peer inside cells to create stop-action movies of proteins and other biomolecules jostling and connecting with each other while mitochondria and other organelles generate energy, assemble new molecules and transport cargo. It is biology in action, a revealing new way to parse the secrets of life that earned its developers the 2017 Nobel Prize in chemistry.

Shengjie Feng, Ph.D., who recently joined Sanford Burnham Prebys as an assistant professor, is an expert in how to leverage the powers of cryo-EM. “My research is truly interdisciplinary,” she says. “I believe that the strong cryo-EM core facility, drug discovery, cancer research and neuroscience research at Sanford Burnham Prebys will play a crucial role in advancing my work.

Feng, who will be part of the Degenerative Diseases program, focuses on the creation and characteristics of ion channels, both in healthy cells and in disease conditions. Ion channels are protein molecules that span the cell membrane, allowing passage of ions (atoms or molecules with a net electric charge, such as sodium, calcium and potassium) from one side of the cell membrane to the other, from outside in or inside out. They are critical to cellular operations, including facilitating communications between cells. Feng has specifically studied ion channels in neural cells.

“We perceive the outer world and construct our inner world through neural circuits in our brain,” she says. “While neurons are the fundamental unit of information integration, responsible for all cognitive behaviors, ion channels serve as the molecular foundation of the electrical signaling that facilitates cell-cell communication. The coordinated opening and closing of these molecules generate a continuous wave of electrical signals throughout the nervous system, which underlies our perception and cognition.

More broadly, Feng notes that ion channel dysfunction is associated with a wide range of diseases, including epilepsy, muscle tension, diabetes and various types of cancers. Approximately 15% of U.S. Food and Drug Administration-approved therapies currently target ion channels as key molecular players.

Cryo-EM density of TMEM16F dimer
Cryo-EM density of TMEM16F dimer, a dual function ion channel and lipid
scramblase (a type of enzyme), with the monomers (molecules that react
with other molecules to form larger molecules or polymers) colored blue
and light blue, respectively, with lipid densities in gray. Image courtesy of
​​​Nature Communications volume 14; article number 4874 (2023).

Yet, these channels remain poorly understood. Feng hopes that by using the visual superpowers of cryo-EM, she can better illuminate their underlying form and function, identifying new drug targets specifically associated with certain diseases.

“I believe that one of the most significant obstacles in neuroscience lies in connecting the molecular level to the circuit level in order to accurately predict the behaviors of neurons and, ultimately, human behavior. 
“With advance in cryo-EM technology, we now have the ability to observe protein complexes in their natural environment at the atomic level. I am optimistic that cryo-EM can serve as the crucial tool needed to bridge the gap between molecular neuroscience and circuit and cognitive neuroscience."

Previously, Feng was a postdoctoral scholar at Howard Hughes Medical Institute and UC San Francisco, where she worked with biophysicist Yifan Cheng, M.D. and neuroscientist Lily Jan, Ph.D.

In Feng’s most recent published work, she helped find a novel drug-binding groove in TMEM16F, an enzyme that moves lipids around in cell membranes that contributes to SARS-Cov-2-induced lung damage. The study is critical for understanding the mechanism of action and for designing drugs that target TMEM16F to potentially help COVID patients with severe symptoms.

Feng earned her Ph.D. in neuroscience at the Institute of Neuroscience, part of the Chinese Academy of Sciences, where she used mouse models to understand the mechanisms and functions of membrane proteins and ion channels during neural development and disease.

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