Bruce Armitage
Professor and Co-Director Carnegie Mellon University
- Pittsburgh PA
Bruce Armitage’s current research interests include the use of PNA for sequence-specific recognition of DNA and RNA.
Biography
Bruce performed his Ph.D. work at the University of Arizona, studying photoinduced electron transfer, energy transfer and polymerization reactions within lipid bilayers under the supervision of Professor David F. O'Brien. After completing his Ph.D. in Chemistry in 1993, he joined Professor Gary B. Schuster's group at the University of Illinois as a postdoctoral fellow, working on the design of new DNA photocleavage agents.
Bruce moved to Georgia Tech with the Schuster group in 1995 to continue this work. Bruce then spent the summer of 1997 in Denmark, working in the labs of Professors Peter E. Nielsen and Henrik Nielsen at the University of Copenhagen, studying the interactions between peptide nucleic acid (PNA) oligomers and RNA.
In August of 1997, Bruce moved to Carnegie Mellon University as an Assistant Professor of Chemistry. He was promoted to Associate and then Full Professor of Chemistry, with courtesy appointments in the Departments of Biological Sciences and Biomedical Engineering. In 2007, Bruce co-founded the Center for Nucleic Acids Science and Technology, which he co-directs with John Woolford of the Department of Biological Sciences. In 2011, Bruce and Danith Ly co-founded PNA Innovations, Inc, a biotechnology startup company that is commercializing gammaPNA technology under an exclusive license from Carnegie Mellon.
Bruce takes great pleasure in teaching undergraduate organic chemistry and graduate courses in medicinal chemistry and sensors. Bruce’s current research interests include the use of PNA for sequence-specific recognition of DNA and RNA and the development of new fluorescence imaging and sensing reagents.
Areas of Expertise
Media
Social
Industry Expertise
Accomplishments
William and Frances Ryan Award for Meritorious Teaching
2011
Carnegie Mellon University
Non-tenured Faculty Award
2001
3M Corp.
National Society of Collegiate Scholars “Outstanding Professor”
2001
Carnegie Mellon Chapter
Julius Ashkin Teaching Award
2004
Faculty and Staff Leadership Award
2003
Education
University of Rochester
B.S.
Chemistry
1988
University of Arizona
Ph.D.
Chemistry
1993
Affiliations
- American Chemical Society journal Langmuir : Senior Editor
Patents
Enhanced biomolecule detection assays based on tyramide signal amplification and gammaPNA probes
US11124822B2
2021-09-21
Provided herein are methods of detecting target analytes, such as nucleic acids, for example microRNAs using an enhanced Tyramide Signal Amplification (TSA) method that employs probes tagged with tyramide-binding groups to amplify the effects of the TSA. The accessibility of the tyramide-binding groups, such as hydroxyphenyl groups, provides for large improvements in signal due to faster reaction with the radicals. The present invention further includes the application of the assay for detecting specific microRNAs.
Nucleic acid-polymer conjugates for bright fluorescent tags
US10982266B2
2021-04-20
A composition includes a polymer including extending chains, side chains, or branches. One (or more) of a plurality of a first strand of nucleic acid is attached to each of a plurality of the side chains. One (or more) of a plurality of a second strand of nucleic acid, which is complementary to the first strand of nucleic acid, is complexed to each of the plurality of the first strand of nucleic acid to form a double strand of nucleic acid on each of the plurality of the side chains. At least one fluorescent compound is associated with the double strand of nucleic acid on each of the plurality of the side chains.
Articles
Targeting a Potential G-Quadruplex Forming Sequence Found in the West Nile Virus Genome by Complementary Gamma-Peptide Nucleic Acid Oligomers
ACS Infectious Diseases2021
In the United States, West Nile virus (WNV) infects approximately 2500 people per year, of which 100–200 cases are fatal. No antiviral drug or vaccine is currently available for WNV. In this study, we designed gamma-modified peptide nucleic acid (γPNA) oligomers to target a newly identified guanine-rich gene sequence in the WNV genome. The target is found in the NS5 protein-coding region and was previously predicted to fold into a G-quadruplex (GQ) structure.
Enhanced Hybridization Selectivity Using Structured GammaPNA Probes
Molecules2020
High affinity nucleic acid analogues such as gammaPNA (γPNA) are capable of invading stable secondary and tertiary structures in DNA and RNA targets but are susceptible to off-target binding to mismatch-containing sequences. We introduced a hairpin secondary structure into a γPNA oligomer to enhance hybridization selectivity compared with a hairpin-free analogue. The hairpin structure features a five base PNA mask that covers the proximal five bases of the γPNA probe, leaving an additional five γPNA bases available as a toehold for target hybridization.
Assembly and Characterization of RNA/DNA Hetero-G-Quadruplexes
Biochemistry2020
Transient association of guanine-rich RNA and DNA in the form of hetero-G-quadruplexes (RDQs) has emerged as an important mechanism for regulating genome transcription and replication but relatively little is known about the structure and biophysical properties of RDQs compared with DNA and RNA homo-G-quadruplexes. Herein, we report the assembly and characterization of three RDQs based on sequence motifs found in human telomeres and mitochondrial nucleic acids.
Enhanced Hybridization Selectivity Using Structured GammaPNA Probes
Molecules2020
High affinity nucleic acid analogues such as gammaPNA (γPNA) are capable of invading stable secondary and tertiary structures in DNA and RNA targets but are susceptible to off-target binding to mismatch-containing sequences. We introduced a hairpin secondary structure into a γPNA oligomer to enhance hybridization selectivity compared with a hairpin-free analogue.
Structural basis for activation of fluorogenic dyes by an RNA aptamer lacking a G-quadruplex motif
Nature Communications2018
The DIR2s RNA aptamer, a second-generation, in-vitro selected binder to dimethylindole red (DIR), activates the fluorescence of cyanine dyes, DIR and oxazole thiazole blue (OTB), allowing detection of two well-resolved emission colors. Using Fab BL3-6 and its cognate hairpin as a crystallization module, we solved the crystal structures of both the apo and OTB-SO3 bound forms of DIR2s at 2.0 Å and 1.8 Å resolution, respectively. DIR2s adopts a compact, tuning fork-like architecture comprised of a helix and two short stem-loops oriented in parallel to create the ligand binding site through tertiary interactions.
Research Focus
Bright Fluorescent Labels Based on DNA Nanostructures
In this project, we use 1D, 2D and 3D DNA nanostructures as scaffolds for the assembly of fluorescent dye arrays. The DNA allows us to concentrate large numbers of dyes within small volumes of space without allowing self-quenching of the dyes. We rely on synthetic organic chemistry to prepare these “DNA nanotags” and then characterize their fluorescence properties by spectroscopy, time-resolved lifetime measurements, single molecule analysis, flow cytometry and microscopy. We collaborate with the Peteanu group on the characterization experiments and with two groups from the Department of Biological Sciences led by Brooke McCartney and Javier Lopez to apply nanotag labels for intracellular protein and RNA detection.
Fluoromodules: A New Class of Fluorescence Imaging Agents Based on Dye-Protein Complexes
The goal of this project is to create a catalogue of fluorescent dye-protein complexes that can be used as genetically encodable labels and biosensors for imaging and detection assays. These “fluoromodules” consist of fluorogenic dyes, i.e. dyes that are nonfluorescent in solution, but become fluorescent when conformationally constrained in some way, and specific protein partners that bind to the dye noncovalently, but with high affinity, leading to strong fluorescence from the dye. Synthetic organic chemistry is used to prepare the fluorogenic dyes, while the protein partners are selected from a library consisting of one billion distinct protein molecules. Once an appropriate protein has been isolated from the library for both strong binding and bright fluorescence activation, the “fluorogen-activation protein”, or FAP, can be genetically fused to a protein of interest. When the protein is expressed inside of a cell or at the cell surface, addition of the fluorgenic dye gives a fluorescent signal to the protein, which can then be imaged and tracked using fluorescence microscopy. This project is part of a larger effort in MBIC that includes significant support from the NIH’s National Technology Centers for Networks and Pathways program. We collaborate closely with Alan Waggoner and Peter Berget of the Department of Biological Sciences and MBIC.
DNA and RNA Recognition by G Quadruplex-Forming Peptide Nucleic Acids
Peptide nucleic acids (PNAs) are synthetic mimics of DNA/RNA in which the hydrogen bonding bases (G,A,C and T) are attached to a peptide-like backbone. Thus, PNA is a chimeric molecule with properties that are reminiscent of both natural proteins and nucleic acids. One of the unique strengths of our department is its development of peptide nucleic acids (PNAs) for applications ranging from chemical biology and biotechnology to nanotechnology and molecular electronics. In most cases, PNAs are designed to have sequences that are complementary to a given DNA or RNA target, allowing the PNA to form a double-helical complex with the target via Watson-Crick base pairing. In collaboration with Danith Ly’s group, we have been designing a special class of PNAs that form “guanine quadruplexes” with specific DNA and RNA targets. This binding mode relies on the PNA and the target nucleic acid to have similar, guanine-rich sequences. Recognition still relies on hydrogen-bond formation, but instead of a G-C pair, the basic unit is a G tetrad, in which the PNA and the DNA/RNA each provide two guanines to a given tetrad. The G-rich target sequences in DNA and RNA have profound biological importance, having been implicated in the regulation of gene expression in diseases ranging from cancer to malaria. Thus, targeting PNAs to these regions should interfere with gene expression, providing important chemical tools for understanding the molecular basis for these diseases and potential therapeutics. We collaborate with Danith Ly on this project.
