242 Chemistry Building
B.S., John Carroll University, 1987
Ph.D., University of Rochester, 1993
Postdoctoral Fellow, University of Colorado, Boulder, 1993-97
Honors and Awards:
C.I. Noll Award for Excellence in Teaching, 2012
Distinguished Honors Faculty Fellow, 2010-2012
Penn State Faculty Scholar Medal in the Physical Sciences, 2010
AAAS Fellow, 2009
Alfred P. Sloan Foundation Fellow, 2001
Camille Dreyfus Teacher-Scholar, 2001
National Science Foundation Career Award, 2000
Kwok, C. K., Sherlock, M. E., and Bevilacqua,
P. C. “Control of RNA Folding Cooperativity by Deliberate Population of
Intermediates in RNA G-Quadruplexes” Angew. Chem. Int. Ed. Engl. 52,
Strulson, C. A., Molden, R. C., Keating, C. D.,* and Bevilacqua,
P. C. “RNA Catalysis Through Compartmentalization”, Nature Chem. 4,
Mullen, M. A., Assmann, S. M.,
Bevilacqua, P. C. “Toward a Digital Gene Response: RNA G-Quadruplexes with
Fewer Quartets Fold with Higher Cooperativity.” J. Am. Chem. Soc. 134,
Nallagatla, S. R., Toroney, R.,
Bevilacqua, P. C. “Regulation of Innate Immunity through RNA Structure and the
Protein Kinase PKR” Curr. Opin. Struct. Biol. 21, 119-127 (2011).
Sokoloski, J. E., Godfrey, S. A.,
Dombrowski, S. E., Bevilacqua, P. C. “Prevalence of syn Nucleobases in
the Active Sites of Functional RNAs.” RNA 17, 1775-1787 (2011).
Ganguly, A., Bevilacqua, P. C.,
Hammes-Schiffer, S. “Quantum Mechanical/Molecular Mechanical Study of the HDV
Ribozyme: Impact of the Catalytic Metal Ion on the Mechanism.” J. Phys.
Chem. Lett. 2, 2906-2911 (2011).
Wilcox, J. L., Ahluwalia, A. K.,
Bevilacqua, P. C. “Charged Nucleobases and Their Potential for RNA
Catalysis.” Accounts Chem. Res. 44, 1270-1279 (2011).
Overview: Biological Chemistry of RNA
The Bevilacqua lab is interested in the folding and catalysis of ribonucleic acid (RNA), and its interactions with proteins. RNA-protein complexes carry out structural and functional roles central to the execution and regulation of many biological processes. Our laboratory focuses on biologically important systems including viral replication and the human viral response, as well as how RNA mediates responses to abiotic stresses in plants. The laboratory is problem based and uses a variety of experimental approaches, some in collaboration as described below, including rapid mixing kinetics, fluorescence spectroscopy, UV melting, site-directed mutagenesis, combinatorial selection of RNA (or SELEX), Raman spectroscopy, NMR, SAXS, and X-ray crystallography. We also apply theory in a number of ways to these problems, including statistical thermodynamics, molecular dynamics (MD), and quantum mechanics. In general, the problems we study lie at the interface of chemistry, biochemistry, biology, and physics.
Characterization of RNA catalysis and folding
The hepatitis delta virus (HDV) is a human pathogen that utilizes a catalytic RNA, or ribozyme, in its replication cycle. We are investigating fundamental catalytic and folding processes of the ribozyme. Mechanistically, we are interested in the role of RNA nucleotides as general acids and bases in the cleavage mechanism. Recent studies in our lab implicate C75 as a general acid in the cleavage mechanism. Current efforts are focused on methods for determining pKa values of critical residues, and examining the effect of individual functional groups and microenvironment on pKa perturbation. In terms of the folding mechanism, we are interested how RNA folds up under in vivo conditions. We have developed collaborations to solve crystal structures of the RNA (with the Golden group at Purdue) and to study the motions of the RNA by molecular dynamics and the reaction pathway by quantum methods (with the Hammes-Schiffer group at UIUC).
Characterization of the RNA-dependent regulation of human viral response
The human double-stranded-RNA-activated protein kinase (PKR) is a 551 residue RNA-binding protein that contains two N-terminal copies of a conserved motif, the double-stranded RNA binding motif (dsRBM), and a C-terminal kinase domain. PKR is present in higher eukaryotes, including humans, and mediates an interferon-induced viral response. We would like to determine the rigorous kinetic mechanism for assembly of an activated PKR complex on dsRNA. Many viruses have evolved strategies for down-regulating PKR. We are examining strategies viral RNAs use to regulate this mechanism. Other issues of interest with PKR include assigning the role of the multiple dsRBMs, and identifying and determining the structure of non-dsRNA sequences involved in regulating PKR activity.
RNA folding in plants as a response to environmental stress
Plants feed the world and are increasingly important sources of fuel and fiber. Unfortunately, approximately half of the global crop yield each year is lost as a result of adverse environmental conditions. Drought is the abiotic stress with the greatest impact on crop yield worldwide and is expected to be exacerbated by global climate change. Plant physiology is also affected by a number of other stressors including salinity, heavy metal ions, and reactive oxygen species. During times of stress, osmolytes and potassium ions accumulate to high concentrations inside of plants. These species are known to generally affect the folding of RNA, which often alters gene expression. We collaborate with the Assmann lab in Biology at Penn State to address these issues. Our overall approach includes discovery and characterization of RNA/DNA switches in plants, including new and novel classes of stress-responsive switches, using a combination of biologically and chemically motivated searches driven by bioinformatics and experiments. These studies are aimed to elucidate key mechanisms for how plants respond to stress at the cellular and molecular levels, and will likely help define mechanisms for gene regulation in response to stress in other eukaryotes.
RNA Folding, Structure, and Catalysis
RNA Folding, Structure, and Catalysis