Biochemistry, Structural Biology
Dr. Yan is a professor in the School of Medicine at Tsinghua University, Beijing, China.
Crossing the Boundary: The Molecular Basis for Electrochemical-Mechanical Coupling of Membrane Transport Proteins
Nieng Yan dreams of becoming a movie producer. Not a red-carpet, Hollywood star, but a creator of movies that reveal the intricate motion of molecules inside living cells. Yan finds beauty in the tiniest details of biology and wants to share that with others. She has already created static images of pumps on the cellular membrane that use energy to move molecules in and out of cells. Next, she wants to show the world the pumps’ movements. The pumps that Yan studies, and ones related to them, are mutated in a number of diseases and understanding their fluid motion could help design drugs to fix them.
As Yan began her undergraduate studies in biology at Tsinghua University in Beijing, science was emerging as a leading industry in China. Believing their daughter could make important contributions in this growing field, Yan’s parents urged her to pursue a career as either a doctor or a scientist.
“I wasn’t sure what I wanted to do myself until one summer as an undergraduate I worked in a structural biology lab,” she says. “As soon as I saw the beautiful crystals and the elegant structures of molecules, I was hooked.”
In that lab, Yan learned how to use X-ray crystallography to determine the arrangement of atoms within a molecule. The technique relies on the fact that when light shines through a crystal, it scatters in different patterns depending on the arrangement of molecules inside. Biological molecules can be turned into crystals by purifying them and letting the surrounding liquid slowly evaporate.
As a graduate student at Princeton University, Yan used X-ray crystallography to see the structure of a handful of proteins involved in cell death in the nematode Caenorhabditis elegans. Those structures revealed how one protein, EGL-1, binds to another, CED-9, to activate a linear pathway that eventually causes cells to self-destruct.
After Yan completed her Ph.D., her Princeton advisor, Yigong Shi, convinced her to stay on for a postdoctoral fellowship by presenting her with a new task—solving the structure of a protein embedded inside the plasma membrane of a cell. “For structural biologists, membrane proteins represent the most challenging targets,” Yan says. “I couldn’t turn down the challenge.”
Yan spent two years studying the structure, learning how to work with finicky membrane proteins. But before she could finish the project, she was offered a position at Tsinghua University in Beijing. At the age of 30, she became the youngest professor at her alma mater. She turned the research over to her Princeton labmates and returned to China.
Her work with membrane proteins was far from finished, however. Once settled in her new lab at Tsinghua, Yan set out to study the structures of transporters and channels—proteins that move molecules in and out of cells through the plasma membrane. That was in 2007. Yan has since found the crystal structures of three key transport proteins involved in moving nutrient molecules.
“These transport proteins are the customs officers for the cells,” she says. “They can very specifically select what they want to bring across in each direction.”
Working with an interdisciplinary team of scientists, Yan is attempting to figure out the structures of glucose transporters, information vital to the study of diabetes and some cancers. “Most cells rely on glucose as their major nutrient. The uptake of glucose is absolutely essential for life,” Yan says. Ultimately, she wants to create not just static images of the transporters but a series of images that illustrate changes that occur as transporters pump materials through the membrane.
“These transporters are very dynamic,” Yan notes. “It’d be great if we could capture many different structures of a transporter and make a continuous movie of how it moves through cycles.” Such a documentary, she adds, would offer a three-dimensional view of a protein’s structure, information that could help in the development of drugs designed to block or activate a particular protein.