Philip James Farabaugh
Professor · Tenured
Department of Biological Sciences
College of Natural and Mathematical Sciences
He/Him/His/Himself
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).
Education
- Postdoc, Genetics — Cornell University (1981)
-
Ph D, Biochemistry
— Harvard University (1978) The lacI gene: sequence of the gene and mutational hotspots
- BA, Biology — University of California San Diego (1972)
Publications
- An evolutionarily conserved phosphoserine-arginine salt bridge in the interface between ribosomal proteins uS4 and uS5 regulates translational accuracy in Saccharomyces cerevisiae 2024
- Post-transcriptional modification to the core of tRNAs modulates translational misreading errors 2024
- The problem of genetic code misreading during protein synthesis 2019
- Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae 2018
- Mutations of ribosomal protein S5 suppress a defect in late-30S ribosomal subunit biogenesis caused by lack of the RbfA biogenesis factor. 2015
- Protein mistranslation: friend or foe? 2014
- Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors 2014
- Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast 2013
- A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae 2010
- BUD22 affects Ty1 retrotransposition and ribosome biogenesis in Saccharomyces cerevisiae 2010
- Accuracy modulating mutations of the ribosomal protein S4-S5 interface do not necessarily destabilize the rps4-rps5 protein-protein interaction 2009
- Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes 2006
- Translational accuracy during exponential, post-diauxic and stationary growth 2004
- Transfer RNA modifications that alter +1 frameshifting in general fail to affect −1 frameshifting 2003
- Shifty ciliates: frequent programmed translational frameshifting in Euplotids 2002
- Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding 2002
- Programmed +1 translational frameshifting in the yeast Saccharomyces cerevisiae results from disruption of translational error correction. 2001
- Programmed translational frameshifting and phenotypic suppression by mutant tRNAs: a reappraisal 2000
- Near–cognate peptidyl–tRNAs promote +1 programmed translational frameshifting in yeast 1999
- How translational accuracy influences reading frame maintenance, 1999
- A new model for phenotypic suppression of frameshift mutations by mutant tRNAs 1998
- Programmed translational frameshifting 1996
- Programmed translational frameshifting 1996
- Special Peptidyl-tRNA Molecules Can Promote Translational Frameshifting without Slippage 1994
- Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site 1990
Presentations
- The pattern of misreading error frequencies in vivo supports a molecular mimicry model for tRNA misreading 2018
- Control of translational missense errors in Saccharomyces cerevisiae by phosphorylation of Ser176 of ribosomal protein uS5 by both Ctk1 and Tor/Pkc1 pathways 2018
Grants and Contracts
- Synthetic Gene Circuits to Measure and Mitigate Translational Stress During Heterlogous Protein Expression 2016
- Synthetic gene circuits to measure and mitigate translational stress during heterologous protein expression 2016
- Role of phosphorylation of ribosomal proteins in translational accuracy 2013
- 2013 Teacher Quality in Biology Program at UMBC 2012
- The UMBC GAANN Doctoral Program in the Biological Scienc 2012
- ARRA: Molecular genetics of translational accuracy 2009
- Molecular genetics of translational accuracy 2007
- Molecular Basis of Translational Recoding in Yeast 1989
- Molecular Basis of Translational Recording in Yeast 1989