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Philip
Bevilacqua
Distinguished Professor of Chemistry and of Biochemistry and Molecular Biology
phil

PhilProfessional Appointments and Affiliations

Distinguished Professor of Chemistry

DIstinguished Professor of Biochemistry and Molecular Biology

Department Head, Chemistry

Office

242 Chemistry Building
University Park, PA 16802

Education

B.S., John Carroll University, 1987

Ph.D., University of Rochester, 1993

Postdoctoral Fellow, University of Colorado, Boulder, 1993-97

Honors and Awards

2019 Swiss RNA Biology Programme Speaker at ETH Zurich and University of Bern

2019 Keynote Speaker, International Symposium RNA Tool and Target. Duke University, Durham, NC

2018 Keynote Speaker, CMBP/RNA Biology Symposium, Ohio State University

2018 Priestley Teaching Prize

2018 Distinguished Professor

2018 Gomberg Lecturer, U Michigan, Ann Arbor MI

2016 Keynote Speaker, Zing Nucleic Acids Conference, Tampa, FL

2015 CESE Tombros Education Fellow

2014 Invited Speaker at RiboClub, Sherbrooke Québec

2013 Keynote Speaker at RNA Upstate NY: Finger Lakes RNA Conference

2012 C. I. Noll Award for Excellence in Teaching

2010 - 2012 Distinguished Honors Faculty Fellow

2010 Penn State Faculty Scholar Medal in Physical Sciences

2009 Elected Fellow of American Association for Advancement of Science (AAAS)

2001 - 2006 Camille Dreyfus Teacher-Scholar

2001 - 2006 Alfred P. Sloan Foundation Fellow

Research

Our lab works to attain a molecular level understanding of RNA in biology.  We find RNA fascinating because it is a both a structural and informatic molecule.  RNA is single stranded and so folds back on itself.  This leads it to adopt simple secondary structures such as stem-loops, as well as complex tertiary structures with clefts that bind small molecules specifically and tightly (riboswitches) and catalyze reactions (ribozymes).  This diversity of structures gives rise to diversity of functions including the ability of RNA to regulate genes.

Ribozyme Mechanism

In the early 1980s, Tom Cech and Sidney Altman showed that RNA could act as an enzyme–a ‘ribozyme’–catalyzing the making and breaking of covalent bonds. This led to the 1989 Nobel Prize in Chemistry. The Bevilacqua lab helped establish roles for nucleobases in proton transfer, determination of driving forces for pKa shifting, and establishing multichannel pathways for RNA cleavage by a combination of experiments and classical and quantum mechanical theory. We are currently working in the HDV and glmS ribozymes to determine roles of metal ions, nucleobases, and cofactors in the mechanism of cleavage of the catalytic RNAs [1-5].  We are collaborating with Sharon Hammes-Schiffer’s lab to perform molecular dynamics and quantum calculations on these ribozymes.  In addition, the lab is focused on how these RNAs fold under in vivo conditions.

RNA Folding In Vivo

Folding of RNA in the cell is not well understood nor has it been integrated into a cohesive mechanistic framework.  We are taking two approaches to understanding RNA folding in vivo(1) Simulating in vivo conditions and examining the RNA folding pathways and the evolutionary driving forces for these, and (2) Determining RNA folding transcriptome-wide in living organisms (plants, bacteria, and archaea) and evaluating implications of this folding on gene regulation and RNA processing.  The former project has the advantage that one can precisely control experimental variable such as crowding, cosolutes, and ionic conditions on RNA folding, while the latter allows observations to be made made directly in a living organism.

Early Earth and RNA

One of the great questions facing humanity is “How did life begin?” It is thought that RNA may have played a major role in the process through the so-called RNA world hypothesis.  We are collaborating with Christine Keating’s lab at Penn State to address physical means that may have aided the emergence of life through the localization and improvement of catalysis.  We are evaluating compartmentalization driven by aqueous phase separation as a potential physicochemical mechanism to concentrate and help chaperone the folding, multiple turnover, and evolution of rare catalytic RNA molecules.  We are also addressing how compartmentalization may facilitate the assembly of progenitor membranes as a step towards protocell formation.  Accomplishing these goals will provide insight into the early evolution of life on this and other planets.

Recent Publications

Poudyal, R., Keating, C. D., Bevilacqua, P. C. Polyanion-assisted catalysis inside complex coacervates. ACS Chem. Biol. 14, 1243-1248. [PubMed] (link to 50 free e-prints).

Yamagami, R., Kayedkhordeh, M., Mathews, D.H., Bevilacqua, P.C. Design of highly active double-pseudoknotted ribozymes: a combined computational and experimental study. Nucleic Acids Res. 47, 29-42 (2019) [PubMed] (open access).

Mitchell III, D., Renda, A.J., Douds, C.A, Babitzke, P., Assmann, S.M., Bevilacqua, P.C. In vivo structural probing of uracil and guanine base pairing by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) RNA 25, 147-157 (2019) [PubMed].

Su, Z., Tang, Y., Ritchey, L.E., Tack, D.C., Zhu, M., Bevilacqua, P. C., Assmann, S. M.  Genome-wide RNA structurome reprogramming reveals temperature-dependent regulation. Proc. Natl. Acad. Sci. 115, 12170-12175 (2018) [PubMed] (open access).

Messina, KJ & Bevilacqua, PC. Cellular small molecules contribute to twister ribozyme catalysis. J. Am. Chem. Soc. 140, 10578-10582 (2018) [PubMed] (link to 50 free e-prints).

 Yamagami R, Bingaman JL, Frankel EA, Bevilacqua PC.  Cellular conditions of weakly chelated magnesium ions strongly promote RNA stability and catalysis. Nat. Commun. 9, 2149  (2018) [PubMed] (open access).

Leamy KA, Yennawar NH, Bevilacqua PC. Molecular mechanism for folding cooperativity of functional RNAs in living organisms. Biochemistry 57, 2994-3002 (2018). [PubMed] (link to 50 free e-prints).

Frankel, E.A. & Bevilacqua, P.C. “Complexity in pH-dependent ribozyme kinetics: Dark pKa shifts and wavy rate-pH profiles.” Biochemistry 57, 483-488 (2018) [PubMed] (link to 50 free e-prints)

Seith, D., Bingaman, J. L., Veenis, A.J., Button, A.C., & Bevilacqua, P. C. “Elucidation of catalytic strategies of small nucleolytic ribozymes from comparative analysis of active sites.” ACS Catalysis 8, 314-327 (2018) [link] (link to 50 free e-prints).