Chemistry 3 3 175

Timea Fernandez

Assistant Professor

CP 409N  Phone: 765-285-2195  

Department of Chemistry
Ball State University
Cooper Physical Science Building, room 305
Muncie, IN 47306

Postgraduate Research Associate Rosalind Franklin University (2007)
Postgraduate Research Associate University of Chicago (2004)
Eotvos Lorand University Ph.D. (2000)
Eotvos Lorand University B.A. (1997) 

Research interests
My laboratory uses fluorescent spectroscopy, nucleic acid footprinting and X-ray crystallography to understand the structural underpinnings of RNA-dependent regulation of gene expression with special attention to genes that are involved in antibiotic resistance in pathogenic bacteria (Figure 1).

Understanding gene expression regulation by the ykkCD riboswitch
Riboswitches are RNA aptamers that regulate gene expression via allosteric structural changes triggered by binding of a small molecule. Most identified riboswitches specifically recognize the metabolic product of the gene to be regulated. When the metabolite concentration reaches a threshold it binds to the riboswitch causing a structural change that in most cases turns off transcription or translation of the metabolite-producing gene

Contrary to most riboswitches, ykkCD is expected to have a broad binding specificity to up-regulate expression of an efflux pump (also called ykkCD) that exports toxic drugs from the bacterial cell. Thus efflux pumps, in addition to antibiotic altering enzymes, play an important role in bacterial antibiotic resistance (Figure 1). The common feature among efflux pump substrates is that they are aromatic cations. Since substrates of the efflux pump are toxic to the bacterial cell, we posit that the ykkCD riboswitch might work as a toxin sensor and could serve as a target in the fight against bacterial pathogens.
Ongoing projects in the laboratory include: (a) determining the substrate specificity of ykkCD using an antibiotic library; (b) test whether gene expression regulation happens at the trascnription or translation stage; (c) decipher the structural changes that occur in response to antibiotic binding.

Gérczei, T. and Correll, C.C. Mechanistic characterization of a site-specific RNA chaperone assembly that is essential for ribosome biogenesis. (under review)
Gérczei, T. and Correll, C.C. (2004) Imp3p and Imp4p mediate an essential U3-pre-rRNA hybridization, presumably to recruit the small subunit processome to the pre-rRNA. Proc Natl Acad Sci U S A 101, 15301-15306.
Correll, C.C. Yang, X. Gerczei, T. Beneken, J. Plantinga, M. J. (2004) RNA recognition and base flipping by the toxin sarcin. J Synchrotron Radiat11, 93-96.
Yang, X. Gerczei, T. Glover, L. T. Correll, C. C. (2001) Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping. Nat Struct Biol 8, 968-973.
Gerczei T, Fazekas A. and Keseru G (2000) Theoretical Study on the Nitric Oxide Binding to Nitrophorin 1, an NO-carrier. THEOCHEM 503, 51-58.
Gerczei, T. Keseru, G. M. Naray-Szabo, G. (2000) Construction of a 3D model of oligopeptidase B, a potential processing enzyme in prokaryotes. J Mol Graph Model 18, 7-17, 57-18.
Gerczei, T. et al. (1999) Conservative electrostatic potential patterns at enzyme active sites: The anion-cation-anion triad. Journal of Chemical Information and Computer Sciences 39, 310-315.
Gerczei, T. Bocskei, Z. Keseru, G. M. Samu, E. Huszthy, P. (1999) Enantiomeric recognition of alpha-(1-naphthyl)ethylammonium perchlorate by enantiomerically pure dimethylphenazino-18-crown-6 ligand in solid and gas phases. Tetrahedron-Asymmetry 10, 1995-2005.
Gerczei, T. Bocskei, Z. Szabo, E. Asboth, B. Naray-Szabo, G. (1999) Structure determination and refinement of the Al3+ complex of the D254,256E mutant of Arthrobacter D-xylose isomerase at 2.40 A resolution. Further evidence for inhibitor-induced metal ion movement. Int J Biol Macromol 25, 329-336. 

Naray-Szabo, G. and Gerczei T. (1996) The (-+-) charge distribution: A common pattern in the transition state of some enzymes. Croatica Chemica Acta 69, 955-965.
Bocskei, Z. Gerczei, T. Bodor, A. Schwartz, R. and Naray-Szabo, G. (1996) Three testosterone derivatives. Acta Crystallographica Section C-Crystal Structure Communications 52, 2899-2903.