Philip J Farabaugh
Professor
Biological Sciences
Biological Sciences Bldg BS 478 (BIOL Main Office)
Education
Postdoc Cornell University 1981
Ph D Harvard University 1978
BA University of California San Diego 1972
About
I earned a B.A. in Biology (UC San Diego, 1972), a Ph.D. in Biochemistry (Harvard University, 1978) and trained as a postdoctoral fellow in Genetics (Cornell University, 1978-1981). I use molecular genetics, mainly, to study how cells (yeast, bacteria or mammalian cells) avoid mistakes in translating RNA into protein. In translating a gene into a protein three nucleotide words (“codons”) are interpreted into amino acids; since there are multiple frames in which genes can be read, errors can result from losing register with the gene (“frameshifting”). Other errors result from incorrectly decoding a codon (“misreading”). These errors can have dire effects on cellular health and, in humans, lead to neurodegeneration and cancer, among other outcomes.
Research Interests
Our laboratory has been concerned with odd events that occur during protein synthesis. We originally discovered programmed +1 translational frameshifting in the Ty family of retrotransposons about 30 years ago and spent many years thoroughly exploring its mechanism. At the end of that work, we discovered we had been studying how the Ty elements manipulated the translation system to drastically increase the frequency of translational errors by forcing decoding by an "incorrect" tRNA—one that makes fewer than three base pairs with the mRNA. We became intrigued with the associated issue of "misreading", where incorrect tRNAs are occasionally accepted into the ribosome resulting in an incorrect protein being produced. Our work has identified a general mechanism responsible for these errors in which non-Watson/Crick base pairs mimic the structure of the standard A•U and G•C pairs, forcing errors that cause specific misreading errors at high frequency. We continue to explore the mechanism(s) underlying these errors and the ways the cell ensures that their frequency doesn't get out of hand.
Teaching Interests
As a molecular geneticist, I have taught a range of courses from the introductory level (BIOL 100 Concepts of Biology, BIOL 302 Molecular and General Genetics), advanced (BIOL 414/614 Eukaryotic Molecular Genetics, BIOL 426/626 Approaches to Molecular Biology) and graduate seminars (BIOL 770 - Graduate Seminar in Molecular Biology).
Contracts, Fellowships, Grants, and Sponsored Research
Farabaugh, Philip J. “Molecular Basis of Translational Recoding in Yeast,” Grant (Funded). Sponsored By: National Institute of General Medical Sciences, NIH. (Aug 1, 1989 – Mar 31, 2007).
Farabaugh, Philip J. “Molecular Basis of Translational Recording in Yeast,” Grant (Funded). Sponsored By: National Institute of General Medical Sciences, NIH. (Aug 1, 1989 – Mar 31, 2007).
Farabaugh, Philip J. “Molecular genetics of translational accuracy,” Grant (Funded). Sponsored By: National Institute of General Medical Sciences, NIH. (May 15, 2007 – Apr 30, 2009).
Farabaugh, Philip J. “ARRA: Molecular genetics of translational accuracy,” ARRA - Recovery Act (Funded). Sponsored By: National Institute of General Medical Sciences, NIH. (Jul 20, 2009 – Jun 30, 2012).
Farabaugh, Philip J. “The UMBC GAANN Doctoral Program in the Biological Scienc,” Grant (Funded). Sponsored By: U.S. Department of Education. (Aug 16, 2012 – Aug 15, 2015).
Farabaugh, Philip J. “2013 Teacher Quality in Biology Program at UMBC,” Grant (Funded). Sponsored By: Maryland Higher Education Commission, Improving Teacher Quality. (Nov 27, 2012 – Mar 31, 2014).
Farabaugh, Philip J. “Role of phosphorylation of ribosomal proteins in translational accuracy,” Sponsored Research (Funded). Sponsored By: UMBC-SRAIS. (Jul 1, 2013 – Jun 30, 2014).
Farabaugh, Philip J. (Co-Principal), Stansfield, Ian (Co-Principal). “Synthetic gene circuits to measure and mitigate translational stress during heterologous protein expression,” Grant (Funded). Sponsored By: National Science Foundation. (Jul 30, 2016 – Jul 30, 2020).
Farabaugh, Philip J. “Synthetic Gene Circuits to Measure and Mitigate Translational Stress During Heterlogous Protein Expression,” Grant (Funded). Sponsored By: NSF. (Aug 1, 2016 – Jul 31, 2021).
Intellectual Contributions
Joshi, Kartikeya, Luisi, Brooke, Wunderlin, Grant, Saleh, Sima, Lilly, Anna, Okusolubo, Temiloluwa, Farabaugh, Philip J. (2024). An evolutionarily conserved phosphoserine-arginine salt bridge in the interface between ribosomal proteins uS4 and uS5 regulates translational accuracy in Saccharomyces cerevisiae. Nucleic Acids Research.
Saleh, Sima, Farabaugh, Philip J. (2024). Post-transcriptional modification to the core of tRNAs modulates translational misreading errors. 1. 30 37-51 Cold Spring Harbor, New York 11724: RNA Journal.
Joshi, Kartikeya, Cao, Ling, Farabaugh, Philip J. (2019). The problem of genetic code misreading during protein synthesis. Online before print Oxford: Yeast.
Joshi, Kartikeya, Trivedi, Monika, Farabaugh, Philip J. (2018). Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae. Nucleic Acids Research.
Nord, S, Bhatt, M J., Tükenmez, H, Farabaugh, Philip J., Wikström, P M. (2015). Mutations of ribosomal protein S5 suppress a defect in late-30S ribosomal subunit biogenesis caused by lack of the RbfA biogenesis factor.. 8. 21 1454-68 RNA (New York, N.Y.).
Ribas de Pouplana, Liuís, Santos, Manuel A. S.., Zhu, Jun-Hao, Farabaugh, Philip J., Javid, Babak. (2014). Protein mistranslation: friend or foe?. 8. 39 355-362 Cambridge, MA: Trends in Biochemical Sciences.
Manickam, Nandini, Nag, Nabanita, Abbasi, Aleeza, Patel, Kishan, Farabaugh, Philip J. (2014). Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors. 1. 20 9-15 Cold Spring Harbor, NY: RNA.
Lamichhane, Tek N., Blewett, Nathan H., Crawford, Amanda K., Cherkasova, Vera A., Iben, James R., Begley, Thomas J., Farabaugh, Philip J., Maraia, Richard J. (2013). Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast. 15. 33 2918-2929 Washington, DC: Molecular and Cellular Biology.
Kramer, Emily B., Vallabhaneni, Haritha, Mayer, Lauren, Farabaugh, Philip J. (2010). A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae. 16 1797-1808 Cold Spring Harbor, NY: RNA.
Dakshinamurthy, Arun, Nyswaner, Karen M., Farabaugh, Philip J., Garfinkel, David J. (2010). BUD22 affects Ty1 retrotransposition and ribosome biogenesis in Saccharomyces cerevisiae. 185 1193-1205 Genetics.
Vallabhaneni, Haritha, Farabaugh, Philip J. (2009). Accuracy modulating mutations of the ribosomal protein S4-S5 interface do not necessarily destabilize the rps4-rps5 protein-protein interaction. 15 1100-1109 Cold Spring Harbor, NY: RNA.
Vallabhaneni, Haritha, Fan-Minogue, Hua, Bedwell, David M., Farabaugh, Philip J. (2009). Connection between stop codon reassignment and frequent use of shifty stop frameshifting. 15 889-897 Cold Spring Harbor, NY: RNA.
Salas-Marco, Joe, Fan-Minogue, Hua, Kallmeyer, Adam K., Klobutcher, Lawrence A., Farabaugh, Philip J., Bedwell, David M. (2006). Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes. 2. 26 438-447 Molecular and Cellular Biology.
Stahl, Guillaume, Ben Salem, Samia N., Chen, Lifeng, Zhao, Bing, Farabaugh, Philip J. (2004). Translational accuracy during exponential, post-diauxic and stationary growth. 3 331-338 Eukaryotic Cell.
Urbonavicius, Jaunius, Stahl, Guillaume, Durand, Jérome M., Ben Salem, Samia N., Qian, Qiang, Farabaugh, Philip J., Björk, Glenn R. (2003). Transfer RNA modifications that alter +1 frameshifting in general fail to affect -1 frameshifting. 6. 9 760-768 RNA.
Klobutcher, Lawrence A., Farabaugh, Philip J. (2002). Shifty ciliates: frequent programmed translational frameshifting in Euplotids. 111 763-766 Cell.
Stahl, Guillaume, McCarty, Gregory P., Farabaugh, Philip J. (2002). Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding. 27 178-183 Trends Biochem Sci.
Stahl, G, Ben Salem, S, Li, Z, McCarty, G, Raman, A, Shah, M, Farabaugh, Philip J. (2001). Programmed +1 translational frameshifting in the yeast Saccharomyces cerevisiae results from disruption of translational error correction.. 66 249-58 Cold Spring Harbor symposia on quantitative biology.
Farabaugh, Philip J. (2000). Programmed translational frameshifting and phenotypic suppression by mutant tRNAs: a reappraisal. 64 131-170 Prog Nucl Acid Res Mol Biol.
Sundararajan, Anuradha, Michaud, William A., Qian, Qiang, Stahl, Guillaume, Farabaugh, Philip J. (1999). Near–cognate peptidyl–tRNAs promote +1 programmed translational frameshifting in yeast. 4 1005-1015 Mol Cell.
Farabaugh, Philip J., Björk, Glenn R. (1999). How translational accuracy influences reading frame maintenance,. 18 1427-1434 EMBO J.
Qian, Qiang, Li, Ji Nong., Zhao, Hong, Hagervall, Tord, Farabaugh, Philip J., Björk, Glenn R. (1998). A new model for phenotypic suppression of frameshift mutations by mutant tRNAs. 1 471-482 Mol Cell.
Farabaugh, Philip J. (1996). Programmed translational frameshifting. 30 507-528 Annu Rev Genetics.
Farabaugh, Philip J. (1996). Programmed translational frameshifting. 60 103-134 Microbiol Rev.
Vimaladithan, Arunachalam, Farabaugh, Philip J. (1994). Special peptidyl–tRNA molecules promote translational frameshifting without slippage. 14 8107-8116 Mol Cell Biol.
Farabaugh, Philip J., Zhao, Hong, Vimaladithan, Arunachalam. (1993). A novel programmed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: frameshifting without tRNA slippage. 1. 74 93-103 Cell.
Belcourt, Michael, Farabaugh, Philip J. (1990). Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site. 62 339-352 Cell.
Presentations
Farabaugh, Philip J. (Author & Presenter), Joshi, Kartikeya (Author), Cao, Ling (Author), Bhatt, Monika (Author), Manickam, Nandini (Author). 27th tRNA Conference. Poster. "The pattern of misreading error frequencies in vivo supports a molecular mimicry model for tRNA misreading," International Union of Biochemistry and Molecular Biology. (Sep 23, 2018).
Joshi, Kartikeya (Author), Bhatt, Monica J. (Author), Farabaugh, Philip J (Author & Presenter). Translational Control. Poster. "Control of translational missense errors in Saccharomyces cerevisiae by phosphorylation of Ser176 of ribosomal protein uS5 by both Ctk1 and Tor/Pkc1 pathways," Cold Spring Harbor Laboratory. (Sep 4, 2018).