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Dr. Rick Russell, Assistant Professor of Biochemistry, is interested in RNA folding and misfolding. As often as proteins misfold, RNAs seem to take the cake at being good at it. Because of their wayward nature, they get a little help from chaperone proteins, which interact with RNAs as they fold to help them find their native states. However, this is a very new field and relatively little is known about RNA folding, much less about how these chaperones work. The first group of RNAs to have demonstrated a need for chaperones is called group I introns. “The big breakthrough came right before I started my lab by Dr. Lambowitz’s lab, where they were the first to demonstrate that one protein actually functions as an RNA chaperone: CYT-19,” he said. This is a DEAD box protein, which are thought to use energy from ATP binding and hydrolysis to help RNA change its conformation. These proteins are implicated in almost everything RNA does, and scientists have speculated that some of these proteins may be RNA chaperones ever since their discovery nearly two decades ago. “A whole field has grown up trying to understand what these DEAD box proteins do and although they are genetically linked to a myriad of RNAs and cellular processes, understanding physically what they do is harder.” The folding process for RNA is incredibly complicated – in principle each molecule has the potential to adopt a larger number of different conformations than there are atoms in the universe. Deciphering which of these are actually formed, and how chaperones deal with the structures that are misfolded, is a daunting challenge. To get at this, Russell’s lab combines traditional biochemical approaches with single molecule detection, which allows them to look at RNA molecules one at a time. Russell compares the field of RNA folding and misfolding to the study of protein folding mechanisms years ago, before there was an understanding of protein misfolding diseases such as Mad Cow disease. “The early understanding of the basic properties of protein folding helped researchers that followed understand the biophysics of what can go wrong and cause proteins to misfold and aggregate. These are unique because they are infectious, and the infectious agent is the misfolded protein,” he said. Russell said that in his case, as most likely was the case with the scientists who first began studying protein misfolding when it was a fledgling field, “I’m not thinking so much what disease this will cure but just that these molecular processes are necessary for life and no one really understands how they work. Fundamental knowledge about RNA misfolding will certainly be useful later. Who knows what those uses will be?” Travis Johnson, a graduate student working toward his PhD, has been in Russell’s lab since 2003, when he began as an undergraduate. “The real world applications will come after we understand the RNA folding process and Rick is always true to the data. There’s a strong temptation to say that data are consistent with a favorite model, but consistent is a weak statement. You have to fit the model to the data, not the data to the model,” he said. Russell’s future projects include starting his two young daughters working in the laboratory. The older one, who is two and a half years old, “seems to have a great future in wearing gloves in the lab, she’s already interested. She’s probably not going to like the classic experiment of putting dry ice in a glove to see what happens, though. She doesn’t like loud noises.” |
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