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GSBS Beyond the Bench: Connecting Single Molecules, The Simpsons, and The Nobel Prize

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Author: Brian Stoveken | Category: Beyond The Bench | October 07, 2015

This article was written by Brian Stoveken, GSBS Ambassador and graduate student in the Biology of Aging program. Stay tuned for more articles by Brian for the "GSBS Beyond the Bench" series.  

I was one of the many students at the UT Health Science Center who was fortunate to attend the Annual HSC Presidential Distinguished Lecture with Dr. William E. Moerner.

Dr. Moerner is the winner of the 2014 Nobel Prize in Chemistry, and is known for his work on microscopy.

Dr. Moerner explained that a revolution is afoot in the basic sciences, stemming from tremendous advances in photonics, microscopy, and physical chemistry. 

Honestly, the term “revolution” doesn’t quite capture the magnitude of the ongoing paradigm shift, which reflects a quest to defy a fundamental property of light. One might even describe his journey to the Nobel Prize as that of a scientist challenging the universe, and winning.

So profound and influential were his contributions that even the creators of the Simpsons* took note, picking Dr. Moerner as a probable Nobel Prize winner in the 2010 episode “Elementary School Musical.” No kidding – look carefully at Milhouse’s selection for the Chemistry prize.

Pop-culture references aside, what revolutionary ideas led Dr. Moerner – a student of San Antonio’s own Thomas Jefferson High School – to the Nobel Prize? As it turns out, this revolution is all about resolution – optical resolution in microscopy, to be specific.

Dr. Moerner’s insight began with studies of fluorescence (the process by which excited molecules emit light), and early attempts to use fluorescence to observe single molecules

At first, this may not seem ground-breaking, but consider that our fabric as human beings boils down the intricate interactions between single molecules – proteins, nucleic acids, carbohydrates and lipids. If it were possible to study these components as a dynamic mixture of individual entities, what might we be able to learn about health and disease? 

Initially, many researchers in the physics and chemistry communities didn’t consider such a feat to be possible. Yet Dr. Moerner felt differently, and reasoned that the emission of light from a single molecule could be detected and measured independent of the ensemble of molecules surrounding it. 

Deviating from “ensemble averaging” in measurement could unlock details about the molecular world that were hitherto hidden in probability distributions.

By isolating and observing individual molecules, it becomes possible to accurately infer their positions and plot them with a positional uncertainty of 10 nanometers or less. To understand just how impressive this is, consider that most of our daily activities are conducted at the scale of meters and kilometers. Now imagine studying phenomena nearly a billion times smaller, and having the capability to plot all of those measurements to build an image with nanometer precision.

Welcome to the “nanoscale” world unlocked by “super resolution” microscopy. What are the results of this revolution in microscopy, you might ask? I encourage readers to sample some comparisons here

Essentially, the “blur” created by light diffraction in conventional microscopy is overcome by plotting the individual locations of molecules; each detected using the techniques pioneered by Dr. Moerner, as well as Dr. Eric Betzig and Dr. Stefan Hell who shared in the 2014 Nobel Prize for their contributions. 

At UTHSCSA, investigators affiliated with our Graduate School of Biomedical Sciences and Medical School can access to this Nobel-winning technology through the Optical Imaging Core Facilities

As a proof of principle, we’ve already used this technology to resolve the interaction between pairs of proteins in E. coli – the bacterium responsible for occasional health scares from contaminated food. 

Traditional fluorescence microscopy (left) vs. super-resolution (right).

With several researchers now exploiting super-resolution imaging on our campuses, keep your eyes peeled for even more exciting developments in the near future.

All together now: Vive la resolutión!

*Photo credit:

The "Beyond The Bench" series features articles written by students and postdoctoral fellows at the Graduate School of Biomedical Sciences at The University of Texas Health Science Center San Antonio. 

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