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 & BiochemistryBiography
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
Molecular Biophysics and Biochemistry
ChairDualMolecular, Cellular, and Developmental Biology
ProfessorPrimaryMolecular Biophysics and Biochemistry
ProfessorSecondary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Center for RNA Science and Medicine
- Developmental Therapeutics
- Microbiology
- Molecular Biophysics and Biochemistry
- Molecular Cell Biology, Genetics and Development
- Molecular, Cellular, and Developmental Biology
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
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)
Academic Achievements and Community Involvement
Links & Media
News
- January 01, 2022
WHRY's Undergraduate Fellows: Tomorrow’s Researchers, Clinicians, and Teachers
- April 23, 2021
American Academy of Arts & Sciences Elects Five from School of Medicine
- January 15, 2014
Two Yale faculty members elected to National Academy
- November 08, 2013
Pioneering RNA researcher is elected a member of the National Academy of Sciences
Get In Touch
Contacts
Molecular, Cellular, and Developmental Biology
260 Whitney Avenue, P.O. Box 208103
New Haven, CT 06511-8103
United States