Areas of Expertise
- Mechanistic studies of protein biosynthesis
- B.A. Gustavus Adolphus College, 1992
- Ph.D. Cornell University, 1997
- Postdoc, UC-Santa Cruz, 1997-2003
Our group is interested in how the ribosome works. The ribosome is a large (~2.5 MDa), two-subunit, RNA-based machine that translates the genetic code in all organisms. In recent years, numerous structures of the ribosome and various ribosomal complexes have been determined by X-ray crystallography and cryo-electron microscopy. Today, a primary challenge is to understand how the ribosome moves and how such dynamics govern the various steps of translation. Since the ribosome is the most common target of natural antibiotics, gaining insight on ribosome function may contribute substantially to the development of new antibiotics.
We use a combination of genetic, molecular, and biochemical methods to study protein synthesis in bacteria. Examples of questions under investigation in the laboratory include: (1) Which features of mRNA tune the rate of initiation? And how do the mechanisms of initiation compare among the different bacterial phyla? (2) How do rRNA dynamics contribute to the mechanism of decoding (aminoacyl-tRNA selection)? (3) What roles do nonessential ribosome-associated GTPases play in the cell?
Baez, W.D., Roy, B., McNutt, Z.A., Shatoff, E.A., Chen, S., Bundschuh, R. and Fredrick, K. 2019. Global analysis of protein synthesis in Flavobacterium johnsoniae reveals the use of Kozak-like sequences in diverse bacteria. Nucleic Acids Res. 47, 10477-10488.
Hoffer, E.D., Maehigashi, T., Fredrick, K*, and Dunham, C.M.* 2019. Ribosomal ambiguity (ram) mutations promote the open (off) to closed (on) transition and thereby increase miscoding. Nucleic Acids Res. 47, 1557-1563. (*co-corresponding authors)
Ying, L., Zhu, H., Shoji, S. and Fredrick, K. 2019. Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA 25, 247-254.
Chen, M. and Fredrick, K. 2018. Measures of single- versus multiple-round translation argue against a mechanism to ensure coupling of transcription and translation. Proc. Natl. Acad. Sci. U.S.A. 115, 10774-10779.
Gibbs, M.R., and Fredrick, K. Roles of elusive translational GTPases come to light and inform on the process of ribosome biogenesis in bacteria. Mol. Microbiol. 107, 445-454.
Roy, B., Liu, Q., and Fredrick, K. 2018. IF2 and unique features of initiator tRNAfMet help establish the translational reading frame. RNA Biol. 15, 604-613.
Gibbs, M.R., Moon, K-M., Chen, M., Balakrishnan, R., Foster, L.J., and Fredrick, K. 2017. Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome. Proc. Natl. Acad. Sci. U.S.A. 114, 980-985.
Liu, Q. and Fredrick, K. 2016. Intersubunit bridges of the bacterial ribosome. J. Mol. Biol. 428, 2146-2164.
Ying, L. and Fredrick, K. 2016. Epistasis analysis of 16S rRNA ram mutations helps define the conformational dynamics of the ribosome that influence decoding. RNA 22, 499-505.
Liu, Q. and Fredrick, K. 2015. Roles of helix H69 of 23S rRNA in translation initiation. Proc. Natl. Acad. Sci. U.S.A. 112, 11559-11564.
Fosso, M. Y., Zhu, H., Green, K. D., Garneau-Tsodikova, S., and Fredrick, K. 2015. Tobramycin variants with enhanced ribosome-targeting activity. ChemBioChem 16, 1565-1570.
Fredrick, K. 2015. Another look at mutations in ribosomal protein S4 lends strong support to the domain closure model. J. Bacteriol. 197, 1014-1016.