Biochemistry, Structural Biology
University of California, Berkeley
Dr. Doudna is also a professor of molecular and cell biology and of chemistry at the University of California, Berkeley, where she holds the Li Ka Shing Chancellor's Chair in Biomedical and Health Sciences.
Mechanisms of RNA-Controlled Gene Expression
In the genetic world, DNA often takes the spotlight while RNA works behind the scenes to carry out the complicated operations within a cell, like retrieving information from DNA and using it to build proteins. Increasingly, however, RNA is attracting more attention from scientists because it has proven far more versatile than DNA, despite their chemical similarities.
Indeed, research has shown that RNA can also store genetic information, like DNA, and catalyze chemical reactions, like specialized proteins called enzymes. A growing number of scientists now believe that this biological diversity makes RNA an evolutionary precursor to both DNA and proteins, a theory that may be impossible to prove, acknowledges Jennifer A. Doudna, who specializes in the study of RNA. "I don't think we'll ever be able to prove how life began, but if we can demonstrate in a test tube the ways that RNA can carry out many of the reactions that are required for a living cell, that, in itself, would be a profound discovery," she explained.
Doudna's research focuses on determining the molecular structures of RNA molecules as a basis for understanding their biological function. Her work lays the foundation for understanding the evolution of RNAs and their relationship to the molecules that played a role in early forms of life.
Growing up in Hawaii, Doudna was always fascinated by the way things worked. In high school, she was drawn to chemistry because it allowed her to understand science on a fundamental level. A high school chemistry teacher encouraged this interest, and when Doudna graduated, she knew she wanted to go into chemistry.
Later, her desire to understand biochemistry on a molecular level led Doudna to study catalytic RNAs called ribozymes, first as a graduate student in the laboratory of HHMI investigator Jack W. Szostak at Harvard University, and then as a postdoc in the laboratory of Thomas R. Cech at the University of Colorado at Boulder. It was Cech, former HHMI president, who discovered in 1982 that RNA can also have enzymatic properties—a finding for which he shared the 1989 Nobel Prize in Chemistry.
In Szostak's laboratory, Doudna worked to create self-replicating ribozymes in a test tube, with the goal of observing how these enzymes may have evolved over time. While working on this project, however, Doudna came to realize that if she wanted to engineer ribozymes and understand how they work, she first needed to know what they looked like. So she headed to Tom Cech's lab to crystallize and determine the three-dimensional structure of a ribozyme, something that had never been accomplished before.
This endeavor took far longer than Doudna could have anticipated. She began the work in Cech's lab in 1991 and completed the project at Yale in 1996, where she had moved to become an assistant professor. But the hard work paid off, and Doudna clearly remembers seeing the structure for the first time. "It was an incredible moment of discovery. My heart was racing, and I had chills down my spine," Doudna said.
She has since crystallized other RNAs, including one from a virus that causes a rare form of hepatitis. Solving these structures is helping scientists answer important questions about how RNA molecules are organized and how they function as enzymes. In separate research, she and her colleagues have discovered that the hepatitis C virus, which causes 10,000 deaths each year in the United States, uses an unusual strategy to synthesize viral proteins—a line of research that could lead to new drugs to block the infection without harming body tissues.
Doudna says she is most motivated by the "process of discovery—of having an idea about how something works and setting out to test it. I am intrigued by the many roles of RNA in biology. Understanding the chemical and biochemical basis for this, as well as the ways in which evolution has taken advantage of these properties to involve RNA at every level of gene expression and regulation in cells and viruses is a lifelong pursuit."