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Ronald Breaker believes in nature's inherent elegance. For nearly 20 years, scientists knew that, in the laboratory, certain single-stranded nucleic acids fold into three-dimensional structures called aptamers, which bind to proteins, amino acids, vitamins, metal ions, and other small molecules. They do this so tightly and with such specificity that it seemed surprising evolution had not taken advantage of them. But no one had found aptamers that bind small molecules in an organism, and many believed they did not exist.
Convinced that such a simple means of recognizing specific molecules would not go unnoticed by nature, Breaker resolved to find natural aptamers that function in modern organisms; so far, he has found dozens of regulatory switches that involve aptamers joined to bacterial genes. These domains of messenger RNAs ("riboswitches") bind to metabolites and control genes responsible for biosynthesis of essential compounds. Riboswitches could represent new drug targets and might be used to control the activity of genes inserted into cells as gene therapies.
Breaker is exploring the structural and functional capabilities of these naturally catalytic RNA and DNA molecules. His research led to creation of the first examples of catalytic DNA—called deoxyribozymes. He also developed a method of "in vitro evolution" to create catalytic RNA molecules that do not exist in nature. He may even be able to resurrect RNA enzymes and other functional RNAs that have been extinct for billions of years.
Beyond aiding understanding of the RNA machinery of cells and RNA's role in evolution, Breaker's research contributes to the capability of creating engineered organisms, biocatalysts, and biosensors for industrial applications and molecular computing systems that could be far more compact than today's silicon computers.
Dr. Breaker is also Professor of Molecular, Cellular, and Developmental Biology at Yale University.
RESEARCH ABSTRACT SUMMARY:
Ronald Breaker is discovering how RNA and DNA molecules catalyze reactions and control gene activity in the cell and is artificially evolving molecules that could be used in industry and medicine.
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Photo: Michelle McLaughlin/AP, © HHMI
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