Ò»±¾µÀÎÞÂë

Bruce Armitage

Professor, Department Head, Chemistry
Co-Director, Center for Nucleic Acid Science and Technology

Bio

Courtesy appointment:

• Professor, Biological Sciences

Education

Ph.D., University of Arizona, 1993
NIH Postdoctoral Fellow, University of Illinois, 1993–1994
NIH Postdoctoral Fellow, Georgia Tech, 1995–1997
NSF International Postdoctoral Fellow, University of Copenhagen, 1997

Research

Keywords: Bioorganic chemistry, fluorescent dyes, DNA nanotechnology, molecular evolution, peptide nucleic acids, molecular recognition of DNA/RNA, G quadruplexes

The Armitage group designs and synthesizes peptide nucleic acid (PNA) oligomers for use in biological imaging, sensing and probing. The PNAs recognize specific sequences of DNA and RNA, allowing precise delivery of fluorescent dyes to those target molecules, which can be visualized by microscopy or detected spectroscopically or by flow cytometry. Alternatively, hybridization of a PNA to a DNA or RNA target can interfere with replication, transcription, splicing or translation, resulting in potential tools for understanding how these processes work and therapeutics for treating a variety of genetic and infectious diseases. We are particularly interested in targeting DNA and RNA G quadruplexes, secondary structures that have been implicated in regulating gene expression as well as formation of biomolecular condensates, i.e. “membraneless organelles” that transiently form in cells, often in response to oxidative stress or another stimulus. The ability to probe and disrupt condensates will be invaluable for understanding the biological function of these phase separated compartments.

Prof. Armitage also teaches Hooked: The Molecular Basis of Addiction each fall semester. The course brings together students from all the different colleges at Ò»±¾µÀÎÞÂë to learn about the molecular mechanisms of addiction arising from the abuse of natural and synthetic drugs as well as treatments. In parallel, the course also guides students through the larger societal factors, government regulatory agencies, health care professionals and private interests that play important roles in addiction.

Projects

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.

Publications

γPNA FRET Pair Miniprobes for Quantitative Fluorescent In Situ Hybridization to Telomeric DNA in Cells and Tissue
Alexander Orenstein, April S. Berlyoung , Elizabeth E. Rastede, Ha H. Pham, Elise Fouquerel, Connor T. Murphy, Brian J. Leibowitz, Jian Yu, Tumul Srivastava ,Bruce A. Armitage, Patricia L. Opresko, Molecules 2017, 22(12), 2117

Fluoromodules Consisting of a Promiscuous RNA Aptamer and Red or Blue Fluorogenic Cyanine Dyes: Selection, Characterization, and Bioimaging
Xiaohong Tan, Tudor P. Constantin, Kelly L. Sloane, Alan S. Waggoner, Marcel P. Bruchez, and Bruce A. Armitage
J. Am. Chem. Soc. 2017, 139 (26), 9001-9009 DOI: 10.1021/jacs.7b04211

RNA G-Quadruplex Invasion and Translation Inhibition by Antisense g-Peptide Nucleic Acid Oligomers
Oyaghire, S. N.; Cherubim, C. J.; Telmer, C. A.; Martinez, J. A.; Bruchez, M. P.; Armitage, B. A., Biochemistry 2016, 55, 1977-1988.

Homologous PNA Hybridization to Noncanonical DNA G-Quadruplexes
Kormuth, K. A.; Woolford, J. L. Jr.; Armitage, B. A., Biochemistry 2016, 55, 1749-1757.

Probing of miniPEG-gPNA-DNA Duplex Hybrid Stability with AFM Force Spectroscopy
Dutta, S.; Armitage, B. A.; Lyubchenko, Y. L., Biochemistry 2016, 55, 1523-1528.

Bright Fluorescent Nanotags Based on Bottlebrush Polymers with DNA-Tipped Bristles
Fouz, Munira F.; Mukumoto, Kosuke; Averick, Saadyah; Molinar, Olivia; McCartney, Brooke M.; Matyjaszewski, Krzysztof; Armitage, Bruce A.; Das, Subha R., ACS Central Sci. 2015, 1, 431-438.

In Vitro Reversible Translation Control Using PNA Probes
Canady, T. D.; Telmer, C. A.; Oyaghire, S. N.; Armitage, B. A.; Bruchez, M. P., J. Am. Chem. Soc. 2015, 137, 10268-10275.

Spectral Fine Tuning of Cyanine Dyes: Electron Donor-Acceptor Substituted Analogues of Thiazole Orange
Rastede, E. E.; Tanha, M.; Yaron, D.; Watkins, S. C.; Waggoner, A. S.; Armitage, B. A., Photochem. Photobiol. Sci. 2015, 14, 1703-1712.

Bichromophoric Dyes for Wavelength Shifting of Dye-Protein Fluoromodules
Pham, H. H.; Szent-Gyorgyi, C.; Brotherton, W. L.; Schmidt, B. F.; Zanotti, K. L.; Waggoner, A. S.; Armitage, B. A., Org. Biomol. Chem. 2015, 13, 3699-3710.

Cooperative Hybridization of γPNA Miniprobes to a Repeating Sequence Motif and Application to Telomere Analysis
Pham, H. H.; Murphy, C. T.; Sureshkumar, G.; Ly, D. H.; Opresko, P. L.; Armitage, B. A., Org. Biomol. Chem., 2014, 12, 7345-7354. PMID: 25115693.

Label-Free Molecular Beacons for Biomolecular Detection and Imaging
Tan, X.; Wang, Y.; Armitage, B. A.; Bruchez, M. P., Anal. Chem. 2014, 86, 10864-10869. PMID: 25287123.

Hybridization of G-Quadruplex Forming Peptide Nucleic Acids to Guanine Rich DNA Templates Inhibits DNA Polymerase η Extension
Murphy, C. T.; Gupta, A.; Armitage, B. A., Opresko, P. L., Biochemistry, 2014, 53, 5315-5322. PMID: 25068499.

Appointments

2022–present	Head of Department of Chemistry, Ò»±¾µÀÎÞÂë
2007–present	Professor, Ò»±¾µÀÎÞÂë
2002–2007	Associate Professor, Ò»±¾µÀÎÞÂë
1997–2002	Assistant Professor, Ò»±¾µÀÎÞÂë
1997	NSF International Research Fellow, University of Copenhagen
1995–1996	NIH Postdoctoral Fellow, Georgia Tech
1993–1994	NIH Postdoctoral Fellow, University of Illinois
1993	Ph.D., University of Arizona

Awards and Distinctions

2011	, Ò»±¾µÀÎÞÂë
2010–2012	President of Inter-American Photochemical Society
2009	Co-Chair of 2009 Gordon Research Conference on Photochemistry
2008–present	Senior Editor of American Chemical Society journal Langmuir
2007	Elected to Phi Kappa Phi Honor Society
2004	Julius Ashkin Teaching Award
2003	Faculty and Staff Leadership Award
2001	Non-tenured Faculty Award, 3M Corp.
2001	Carnegie Mellon Chapter National Society of Collegiate Scholars “Outstanding Professor”