Philip Farabaugh
Professor
| Phone |
410-455-3018
|
|---|---|
| farabaug@umbc.edu | |
| Education |
Postdoc, Cornell University (1981)
Ph D, Harvard University (1978)
BA, University of California San Diego (1972)
|
| Website | http://biology.umbc.edu/directory/faculty/person/BS78123/ |
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
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)
Role of phosphorylation of ribosomal proteins in translational accuracy Sponsored Research (Funded) Sponsored by UMBC-SRAIS (Jul 1, 2013 – Jun 30, 2014)
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)
The UMBC GAANN Doctoral Program in the Biological Scienc Grant (Funded) Sponsored by U.S. Department of Education (Aug 16, 2012 – Aug 15, 2015)
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)
Molecular genetics of translational accuracy Grant (Funded) Sponsored by National Institute of General Medical Sciences, NIH (May 15, 2007 – Apr 30, 2009)
Molecular Basis of Translational Recoding in Yeast Grant (Funded) Sponsored by National Institute of General Medical Sciences, NIH (Aug 1, 1989 – Mar 31, 2007)
Molecular Basis of Translational Recording in Yeast Grant (Funded) Sponsored by National Institute of General Medical Sciences, NIH (Aug 1, 1989 – Mar 31, 2007)
Intellectual Contributions
(2019) The problem of genetic code misreading during protein synthesis Oxford Yeast Download.
(2018) Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae Nucleic Acids Research
(2016) Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength. London, England, United Kingdom Nucleic acids research
(2015) Ribosomal protein and biogenesis factors affect multiple steps during movement of the Saccharomyces cerevisiae Ty1 retrotransposon. Mobile DNA
(2015) Mutations of ribosomal protein S5 suppress a defect in late-30S ribosomal subunit biogenesis caused by lack of the RbfA biogenesis factor. RNA (New York, N.Y.)
(2014) Protein mistranslation: friend or foe? Cambridge, MA Trends in Biochemical Sciences
(2013) Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors Cold Spring Harbor, NY RNA
(2013) Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast Washington, DC Molecular and Cellular Biology
(2010) A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae Cold Spring Harbor, NY RNA
(2010) BUD22 affects Ty1 retrotransposition and ribosome biogenesis in Saccharomyces cerevisiae Genetics
(2009) Accuracy modulating mutations of the ribosomal protein S4-S5 interface do not necessarily destabilize the rps4-rps5 protein-protein interaction Cold Spring Harbor, NY RNA
(2009) Connection between stop codon reassignment and frequent use of shifty stop frameshifting Cold Spring Harbor, NY RNA
(2007) The frequency of translational misreading errors in E. coli is largely determined by tRNA competition. RNA (New York, N.Y.)
(2006) Evolution of +1 programmed frameshifting signals and frameshift-regulating tRNAs in the order Saccharomycetales. Journal of molecular evolution
(2006) Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes Mol Cell Biol
(2004) Translational accuracy during exponential, post-diauxic and stationary growth Eukaryotic Cell
(2003) Transfer RNA modifications that alter +1 frameshifting in general fail to affect -1 frameshifting RNA
(2002) Shifty ciliates: frequent programmed translational frameshifting in Euplotids Cell
(2002) Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding Trends Biochem Sci
(2001) Programmed +1 translational frameshifting in the yeast Saccharomyces cerevisiae results from disruption of translational error correction. Cold Spring Harbor symposia on quantitative biology
(2000) Programmed translational frameshifting and phenotypic suppression by mutant tRNAs: a reappraisal Prog Nucl Acid Res Mol Biol
(1999) Near–cognate peptidyl–tRNAs promote +1 programmed translational frameshifting in yeast Mol Cell
(1999) How translational accuracy influences reading frame maintenance, EMBO J
(1998) A new model for phenotypic suppression of frameshift mutations by mutant tRNAs Mol Cell
(1996) Programmed translational frameshifting Annu Rev Genetics
(1996) Programmed translational frameshifting Microbiol Rev
(1994) Special peptidyl–tRNA molecules promote translational frameshifting without slippage Mol Cell Biol
Presentations
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 Strasbourg, France (Sep 23, 2018)
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 Cold Spring Harbor, NY (Sep 4, 2018)