Philip Bevilacqua
Professional Appointments and Affiliations
Distinguished Professor of Chemistry
Distinguished Professor of Biochemistry and Molecular Biology
Department Head, Chemistry (Aug 2018- June 2024)
Education
B.S., John Carroll University, 1987
Ph.D., University of Rochester, 1993
Postdoctoral Fellow, University of Colorado, Boulder, 1993-97
Honors and Awards
Research
2022 Keynote Speaker, Northwestern University T32 Training Grant Symposium
2020 Keynote Speaker, Bermuda Principles
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 Gomberg Lecturer, U Michigan, Ann Arbor MI
2018 Keynote Speaker, CMBP/RNA Biology Symposium, Ohio State University
2018 Distinguished Professor, Penn State
2016 Keynote Speaker, Zing Nucleic Acids Conference, Tampa, FL
2013 Keynote Speaker, RNA Upstate NY: Finger Lakes RNA Conference
2010 Faculty Scholar Medal in Physical Sciences, Penn State
2009 Elected Fellow of American Association for Advancement of Science (AAAS)
2001 - 2006 Camille Dreyfus Teacher-Scholar
2001 - 2006 Alfred P. Sloan Foundation Fellow
2000 - 2005 National Science Foundation (NSF), Faculty Career Development (CAREER) Award
Teaching
2020 Alumni/Student Award for Excellence in Teaching, Penn State University-wide
2018 Priestley Teaching Prize, Penn State Chemistry
2015 CESE Tombros Education Fellow, Penn State
2012 C.I. Noll Award for Excellence in Teaching, Penn State Eberly College
2010 - 2012 Distinguished Honors Faculty Fellow, Penn State Schreyer Honors College
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 twister and other ribozymes to determine roles of metal ions, nucleobases, and cofactors in the mechanism of cleavage of the catalytic RNAs.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. We collaborate with Professors Sally Assmann and Paul Babitzke in the in vivo work.
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
Jolley, E. A., Yakhnin, H., Tack, D. C., Babitzke, P. & Bevilacqua, P. C. Transcriptome-wide probing reveals RNA thermometers that regulate translation of glycerol permease genes in Bacillus subtilis. RNA (in press) (2023). [PubMed].
Sieg J.P., Arteaga S.J., Znosko B.M., Bevilacqua PC. Meltr software provides facile determination of nucleic acid thermodynamics. Biophys Rep 3, 100101 (2023). [PubMed].
Sieg, J. P., McKinley, L. N., Huot, M. J., Yennawar, N. H., Bevilacqua, P. C. The metabolome weakens RNA thermodynamic stability and strengthens RNA chemical stability. Biochemistry 61, 2579-2591 (2022). [PubMed].
Yamagami, R., Sieg, J., Assmann, S. A., Bevilacqua, P. C. Genome-wide analysis of the in vivo tRNA structurome reveals RNA structural and modification dynamics under heat stress. Proc. Natl. Acad. Sci. 119, e2201237119 (2022). [PubMed].
Choi, S., Meyer, M. O., Bevilacqua, P. C., Keating, C. D. Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles. Nature Chem. 14, 1110-1117 (2022). [PubMed].
Bevilacqua, P. C., Williams, A. M., Chou, H. L., Assmann, S. M. RNA multimerization as an organizing force for liquid-liquid phase separation. RNA 28, 16-26 (2022). [PubMed]. 
Veenis, A. J., Li, P., Soudackov, A. V., Hammes-Schiffer, S., Bevilacqua, P. C. Investigation of the pKa of the nucleophilic O2' of the hairpin ribozyme. J. Phys. Chem. B. 43, 11869-11883 (2021). [PubMed].
Leamy, K. A., Yamagami, R., Yennawar, N., Bevilacqua, P. C. Single nucleotide control of tRNA folding cooperativity. Proc Natl. Acad. Sci. 116, 23075-23082 (2019). [PubMed].
Poudyal, R., Keating, C. D., Bevilacqua, P. C. Polyanion-assisted catalysis inside complex coacervates. ACS Chem. Biol. 14, 1243-1248 (2019). [PubMed].
Poudyal, R.R., Guth, R.M., Veenis, A.J., Frankel, E.A., Keating, C.D., Bevilacqua, P.C. Template-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates. Nat. Commun. 10, 490 (2019) [PubMed] (open access).
Messina, KJ & Bevilacqua, PC. Cellular small molecules contribute to twister ribozyme catalysis. J. Am. Chem. Soc. 140, 10578-10582 (2018) [PubMed].