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Ronald Breaker, PhD, BS

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About

Titles

Sterling Professor of Molecular, Cellular, and Developmental Biology and Professor of Molecular Biophysics and Biochemistry

Investigator, Howard Hughes Medical Institute, Molecular, Cellular and Developmental Biology; Chair, Dept Basic Science: Molecular Biophysics & Biochemistry

Biography

Dr. Breaker is a Sterling Professor of the Department of Molecular, Cellular and Developmental Biology at Yale University, is jointly appointed as a professor in the Department of Molecular Biophysics and Biochemistry, and is an Investigator with the Howard Hughes Medical Institute. His graduate studies with Dr. Peter Gilham at Purdue University focused on the synthesis of RNA and the catalytic properties of nucleic acids. As a postdoctoral researcher with Dr. Gerald Joyce at The Scripps Research Institute, Dr. Breaker pioneered a variety of in vitro evolution strategies to isolate novel RNA enzymes and was the first to discover catalytic DNAs or “deoxyribozymes” using this technology. Since establishing his laboratory at Yale in 1995, Dr. Breaker has continued to conduct research on the advanced functions of nucleic acids, including ribozyme reaction mechanisms, molecular switch technology, next-generation biosensors, and catalytic DNA engineering. In addition, his laboratory has established the first proofs that metabolites are directly bound by messenger RNA elements called riboswitches. Dr. Breaker’s research findings have been published in more than 220 scientific papers, book chapters, and patent applications, and his research has been funded by grants from the NIH, NSF, DARPA, the Hereditary Disease Foundation, and from several biotechnology and pharmaceutical companies. He is the recipient of fellowships from the Arnold and Mabel Beckman Foundation, the David and Lucile Packard Foundation, and the Hellman Family Trust. In recognition of his research accomplishments at Yale, Dr. Breaker received the Arthur Greer Memorial Prize (1997), the Eli Lilly Award in Microbiology (2005), the Molecular Biology Award from the U.S. National Academy of Sciences (2006), and the Merck Award from the American Society for Biochemistry and Molecular Biology (2016). Dr. Breaker was inducted into the U.S. National Academy of Sciences in 2014. He has cofounded two biotechnology companies and is a scientific advisor for industry and for various government agencies. He serves on the editorial board for the scientific journals RNA Biology, RNA, and Cell Chemical Biology.

Appointments

Education & Training

Postdoctoral Fellow
The Scripps Research Institute (1995)
PhD
Purdue University, Biology/Biochemistry (1992)
Ph.D.
Purdue University (1992)
BS
University of Wisconsin - Stevens Point, Biology/Chemistry (1987)
B.S.
University of Wisconsin - Stevens Point (1987)

Research

Overview

The Breaker laboratory uses a variety of approaches to explore the
fundamental properties of nucleic acids. For example, the laboratory
develops new techniques for in vitro selection to create new functional
RNAs and DNAs. In vitro selection is patterned after natural Darwinian
evolution, but where "survival-of-the-fittest" is played out at the
molecular level in the absence of living cells. Up to 100 trillion
different molecules can be subjected to this test-tube evolution
process to isolate or engineer molecules that perform tasks such as
catalysis and molecular sensing.

Previous molecular engineering projects have provided evidence that both RNA and DNA have substantial untapped potential for sophisticated biochemical function. For example, we have produced a variety of new DNA enzymes, some that operate under cell-like conditions and perform reactions that mimic important biochemical transformations. In addition, we have generated dozens of examples of RNAs that function as designer molecular switches that respond to specific small molecules. These findings demonstrate that the primary roles of RNA and DNA in nature might be greater than currently appreciated, and suggests that the function of nucleic acids could be expanded via molecular engineering.

Inspired by these molecular engineering demonstrations, we have more
recently begun to search for novel types of non-coding RNAs that
perform undiscovered catalytic or molecular sensing tasks in cells. We
have identified numerous classes of "riboswitches", which are
metabolite-binding mRNA domains that control genes responsible for
biosynthesis of essential compounds. Among the first dozen riboswitches
classes identified are representatives that sense coenzymes,
nucleobases, amino acids or sugars. Some riboswitch classes exhibit
complex biochemical behaviors including ribozyme activity, cooperative
ligand binding, and logic gate function. In addition, we have
identified other non-coding RNAs that are not riboswitches, but whose
biological functions remain to be established. We will continue to use
bioinformatics, genetics, and biochemistry techniques to discover new
types of non-coding RNAs and to establish the functions of these
complex-folded nucleic acids.The Breaker laboratory is working to discover novel non-coding RNAs in all three domains of life. Bioinformatics systems are used to identify candidate structured RNAs, and the functions of these new-found RNAs are validated using genetic and biochemical techniques.

In addition, the Breaker laboratory is exploring the functional capability and utility of nucleic acids when engineered outside the confines of cells.

Medical Subject Headings (MeSH)

Bacteria; Biochemistry; Biology; Biotechnology; Computational Biology; Fungi; Genetics, Microbial; Genomics; Metabolomics; Microbiology; Molecular Biology

Research at a Glance

Yale Co-Authors

Frequent collaborators of Ronald Breaker's published research.

Publications

Featured Publications

2024

Academic Achievements & Community Involvement

  • honor

    Huck Distinguished Lecturer

  • honor

    Member

  • honor

    Sterling Professor

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    Chan Lecture

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    ASBMB-Merck Award

Get In Touch

Contacts

Academic Office Number
Lab Number
Mailing Address

Molecular, Cellular, and Developmental Biology

260 Whitney Avenue, P.O. Box 208103

New Haven, CT 06511-8103

United States

Administrative Support