Published by the Students of Johns Hopkins since 1896
July 8, 2020

Lab Spotlight: Sua Myong

Studying the dance of proteins through chromatography

By TRISHA PARAYIL | November 29, 2018




Myong is the head of the Single Molecule Imaging Lab.

In Sua Myong’s lab, proteins dance.

To hear Myong talk about single molecule detection, her research specialty, one might think that she was describing a ballet.

At its most basic level, single molecule detection involves observing the fine motion of two dye spots: one spot on a protein and one on the substrate DNA or RNA strand that the protein is bound to. The proteins may glide up and down in an accordion motion, twist like a screwdriver or jerk like a can opener.

Researchers at Myong’s Lab, the Single Molecule and Single Cell Imaging Laboratory, are privy to a private performance displaying all these kinds of choreographies.

Myong’s road to single molecule detection was a long one. She studied molecular biology in her undergraduate and graduate years. As a biology student, her research involved taking ensemble measurements, such as measuring the average distance between protein and DNA and RNA strands.

Then, as a post doctoral student in the year 2004, Myong used single cell detection for the first time. When she first saw the measurement, she was shocked. Suddenly she could see each protein’s “dance”: the range of motion, the speed and binding rates of each protein. The static ensemble measurement hid all that movement. 

To Myong, what she observed seemed magical.

Soon after, Myong published a paper, her first using the single molecule technique, describing the back-and-forth movement of a protein, Rad5, in the replication fork in DNA. 

Today, Myong is an associate professor in the Biophysics department.

For some, bedtime brings visions of dancing sugarplums. For Myong it brings molecular choreography. What does the signal that they found in lab today mean? What exactly is the protein structure of the molecule that was dancing?

Most recently the lab examined the protein that unwinds a folding structure in genomic DNA and RNA called G-quadruplex.

The presence of G-quadruplex can perturb genomic processes by simply existing. An RecQ helicase binds to the G-quadruplex and distorts it in a tug-of-war motion.

When it binds to DNA G-quadruplex, the protein moves in a seamless motion. But when it binds to RNA G-quadruplex, the movement is more slow, less fluid. In both cases, the protein rhythmically unwinds and refolds the DNA and RNA.

Recently, a collaborator with the Myong lab discovered the exact structure of the protein.

Myong described it like meeting an overseas pen pal in-person. Just as letters convey a pen pal’s personality, single cell detection hinted at the protein’s structure. The researcher’s conjectures were proven correct in all regards except size — the protein turned out to be much larger than imagined.

The microscopic scale of Myong’s research does not limit the scope of its impact. Myong stays true to her roots as a premed student and, whenever possible, couples cell studies with in vitro studies. While observing the movement of proteins, the lab puts it in the physiological context.

Currently, the biggest project in the lab involves investigating mutations in an RNA binding protein that is linked to amyotrophic lateral sclerosis (ALS).

RNA binding proteins have intrinsically disordered regions in neurons which tend to coagulate and form into liquid particles. But in patients with ALS, the liquid-like properties are lost over time, and the proteins form into fibers and plaques. FUS, which is a specific protein that the lab is examining, has over 70 mutations associated with ALS. The mutations affect the way that the protein interacts with RNA. The protein loses its dynamism and becomes either hindered or completely static. The lab wants to pinpoint exactly when the mutation becomes a disease.

To answer that question, they have to simply cue the music and watch as the molecules take the floor.

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