News & Highlights

The Ultimate Radar Detector

Essentially all chemistry in the Universe occurs at an interface ––David Nesbitt

The Nesbitt group has invented a nifty technique for exploring the physics and chemistry of a gas interacting with molecules on the surface of a liquid. The group originally envisioned the technique because it’s impossible to overestimate the importance of understanding surface chemistry. For instance, ozone depletion in the atmosphere occurs because of chemical reactions of hydrochloric acid on the surface of ice crystals and aerosols in the upper atmosphere. Interstellar chemistry takes place on the surface of tiny grains of dust. And, any time industrial chemists want to react a gas with a liquid or solid, the secret is getting the gas to touch the surface of whatever they want the gas to react with. “At the surface of the ocean, for example,” explained Fellow David Nesbitt, “wave action generates small little liquid droplets that get popped up into the air. This is why it’s such a pleasant experience to be near the ocean, and it’s why we smell the ocean. And, there’s a great deal of chemistry occurs at the interfaces of these microscopic to nanoscopic aerosol particles.” Nesbitt added that it’s even possible that life itself may have originated inside microscopic liquid particles formed early in Earth’s history. Back in present time, however, the new technique will help the group investigate the complex chemistry that occurs on the surface of liquids. For instance, the technique (which Nesbitt has dubbed the ultimate radar detector) can identify the quantum states of new molecules produced in chemical reactions that occur when a supersonic jet of gas molecules interacts with a liquid-like surface called a self-assembled monolayer, or SAM. Some neat things about a SAM are that (1) the SAM sways around like a liquid even though it’s attached to a solid anchor at one end and (2) it’s possible to link different kinds of molecules to it. Different molecules on the SAM will react differently with the same supersonic jet of gas molecules. The new technique is able to not only identify the products of these chemical reactions, but also detect the flight paths and speed of all the molecules that come flying off the SAM. The researchers responsible for inventing the new ultimate radar detection system (which they call Quantum-State Resolved 3D Velocity Map Imaging) are graduate student Carl Hoffman and Fellow David Nesbitt.––Julie Phillips

Custom-Made RNA

New method may lead to the regulation of gene expression, the development new drugs, and improved prospects for gene therapy.

A wildly successful JILA (Nesbitt Group)-NIH collaboration is opening the door to studies of RNA behavior, including binding, folding and other factors that affect structural changes of RNA from living organisms. Such structural changes determine RNA enzymatic functions, including the regulation of genetic information.

Yun-Xing Wang of the National Institutes of Health (NIH) and his collaborators developed a novel method for making small RNA strands consisting of dozens of structural units called nucleotides, and also precisely placed radioactive or fluorescent-dye labels in targeted locations along the RNA strand. Then Fellow David Nesbitt and recent JILA Ph.D. Erik Holmstrom used their lab’s single-molecule Fluorescence Resonance Energy Transfer (smFRET) method to prove that Wang’s innovative method for custom-making RNA worked as advertised

Such studies are critically important in science and medicine. Small RNAs play key roles in the biochemistry inside cells. For example, inside a cell small RNAs called riboswitches regulate the production of proteins encoded by messenger RNA and ribozymes, which can catalyze cellular biochemical reactions. Other small RNAs called aptamers are currently under study for drug development, work many researchers hope will also improve the prospects for gene therapy.

Plus, the ability to custom-make strands of RNA may also lead to the creation of designer drugs and RNA-based molecular sensors. The development of new RNA-based technologies and fundamental research in the biophysics of RNA action in cells will both profit from the new method for custom-making RNA.

The new method employed an automated robotic platform consisting of DNA templates (blueprints for a variety of custom-made RNA strands) bonded to a solid bead. The RNAs produced by the robotic platform were labeled with radioactive isotopes (for NMR studies) or fluorescent dye molecules at specifically determined locations (for smFRET studies). The dye molecules allowed Nesbitt and Holmstrom to show that the RNA strands were folding exactly as predicted, confirming the validity of the method developed by Yu Liu, Jason R. Stagno, Jinfa Ying, and Yun-Xing Wang of the National Institutes of Health and their colleagues from the National Heart, Lung, and Blood Institute; Frederick National Laboratory for Cancer Research; and the University of Texas Health Science Center.—Julie Phillips

Crowd-Folding

Biomolecules may not always behave the same way in test tubes as they do in living cells, a fact underscored by important new work by former research associate Nick Dupuis, graduate student Erik Holmstrom, and Fellow David Nesbitt. The researchers found that under crowded conditions that begin to mimic those found in cells, single RNA molecules folded 35 times faster than in the dilute solutions typically used in test-tube experiments. Crowding also led to a modest decrease in the unfolding rate. The results strongly support the idea that compact structures, such as folded RNA molecules and proteins, may be much more stable in living cells than they are in test tubes, where there’s lots of room to stretch out and flop around.

The Unfolding Story of Telomerase

Graduate student Erik Holmstrom and Fellow David Nesbitt have applied their laboratory research on the rates of RNA folding and unfolding to the medically important enzyme telomerase. Telomerase employs both protein and RNA components to lengthen chromosomes, which are shortened every time they are copied.

If one short piece of the RNA in telomerase is folded into an organized structure called a pseudoknot, then the enzyme works properly. The enzyme repeatedly adds short pieces of DNA to the chromosomes within the cells of people and many other organisms. Because it counteracts the natural shortening of chromosomes, telomerase is vital for keeping cells alive and healthy through multiple cell divisions.

 

RNA folding: The rest of the story

The Nesbitt group has been investigating RNA folding since the early 2000s. The group’s goal has been to gain a detailed understanding of the relationship between structure and function in this important biomolecule. One challenge has been figuring out how unfolded RNA molecules assume the proper three-dimensional (3D) shape to perform their biological activities. To accomplish this, the researchers have shown how biologically active RNA is able to neutralize negative charges that end up in close proximity to each other after folding into a 3D structure.

Way Faster than a Speeding Bullet

The interface between a gas and a solid is a remarkable environment for new investigations. Lots of fascinating chemistry takes place there, including catalysis. Catalysis is acceleration of a chemical reaction that is caused by an element like platinum that remains unchanged by a chemical reaction. For instance platinum catalyzes the transformation of carbon monoxide (CO) into carbon dioxide (CO2) in automobile catalytic converters. A better understanding of catalysis could improve the efficiency of manufacturing important chemicals as well as expanding our fundamental knowledge of chemistry.