Johns Hopkins Professor Saw RNA's Potential When Field Was YoungA sign on the door leading to David Draper's chemistry lab carries an unusual disclaimer: "Caution: you are now entering the RNA world."
It's sort of an inside joke for life sciences cognoscenti. Draper's work focuses on the complex biochemical behavior of RNA, or ribonucleic acid. One theory about the earliest days of evolution proposes that, before the emergence of DNA on Earth some 4 billion years ago, life revolved around RNA instead.
It would have been an "RNA world."
The theory has gained momentum in recent years, as more is learned about the biochemistry of RNA, which has become an increasingly popular field of research. Scientists probing the workings of RNA have been rewarded with Nobel Prizes, and computers are now being used to study how its complicated folding patterns relate to a multitude of functions.
But it wasn't such a sexy field of study 16 years ago, when Draper arrived at The Johns Hopkins University. Just as RNA may have played an essential role in the beginning of life on Earth, Draper, now chairman of the Chemistry Department, has been an important player in the evolution of RNA research.
Shortly after joining the Hopkins faculty in 1980, when it was time for him to decide what kinds of research to concentrate on, he took a scientific gamble. Although there were no techniques for producing large quantities of RNA -- a requirement for its detailed study -- he decided to focus on RNA research.
It has since blossomed into a major field.
"He made the correct decision a long time ago," said one of Draper's colleagues, chemistry professor Craig Townsend.
For Draper, the choice was easy.
RNA is essential in the manufacture of proteins ranging from vital enzymes and hormones to hemoglobin and structural components. DNA, or deoxyribonucleic acid, contains the huge library of genetic information organisms need to reproduce and to make RNA. Both DNA and RNA are made of molecules called nucleotides. But, whereas DNA consists of two strands of nucleotides, bound together in a twisting, ladder-like structure, RNA is made of just a single string of nucleotides.
"DNA is just this monotonous double helix," Draper said, adding that its shape follows a regular pattern that is easily understood. But, because RNA consists of only a single strand, it folds back onto itself in multifarious hairpin loops and numerous shapes that are difficult to predict. The complex patterns are similar to the structures formed when proteins fold into certain shapes that enable them to perform specific functions.
"But the whole issue of RNA folding has not been nearly as well-explored" as protein folding has, Draper said. Consequently, RNA research represents a challenging frontier.
"It's difficult work, but it's what he has decided to do," Townsend said. "I remember him interviewing here, and thinking that this guy is really smart and wants to do incredibly courageous and creative work, but is this someone who would survive in a chemistry department?"
Draper wanted to conduct rigorous studies of RNA's structure, as a chemist analyzes the structures of molecules and organic compounds. But the techniques to adequately pursue such RNA research did not exist.
However, over the past 15 years, major advances in chemistry have bridged the gaps between it and other disciplines, including biology, so that RNA research is squarely in the chemist's domain.
"So much growth has gone on in this field," Townsend said.
Meanwhile, Draper has applied his unusually broad knowledge of chemistry and biological sciences to probe RNA's secrets. He was among a handful of pioneers who figured out how to make large quantities of RNA molecules for research. He has studied the mysterious interplay between RNA and proteins in ribosomes, cellular particles that produce a variety of proteins needed for life.
Findings from research in his lab have shed light on the complicated shapes that RNA molecules fold into.
Most recently, in work aimed at developing better antibiotics, he has made a surprising discovery: a protein that attaches itself to RNA, making it possible for a certain antibiotic to fight bacterial infection, is remarkably similar to a class of proteins that bind to DNA.
Even though they have completely different functions, the proteins have the same general shape, and they use a similar method to bind to RNA and DNA, information that could help scientists in their search for more effective antibiotics.
All of this work has not gone unnoticed; Draper recently received a coveted MERIT award from the National Institutes of Health, which automatically extends his research funding for 10 years. MERIT stands for Method to Extend Research in Time. The awards are given rarely and cannot be applied for. Scientists with exceptional track records are nominated by their NIH funding source.
The decade-long funding eliminates one source of stress in the life of a scientist: reapplying for grant renewals every four years and hoping the funding comes through. Scientists feel pressured to publish a number of scientific papers to show productivity within the grant period.
But 10 years is "practically forever," Draper said. "The idea is that maybe you will go off and do something a little more creative or unusual if you don't have that pressure," he said.
Draper said he may explore how RNA manages to fold into compact shapes.
"Can we start to write computer programs that will predict the stabilities of different RNA folding patterns? That's when I get to the edge of what I know," he said. "That's where the grant comes in. I don't have to worry about a deadline. I can pursue ideas that might not pay off for five years."
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