Superior CONICET researcher / Full Professor UNC
Phone: +54 351 5353855 ext 3433
Molecular mechanisms involved in the maintenance and diversification of the genetic information
Mutation and recombination, sources of genetic diversity, are modulated by evolutionarily conserved physiologic processes, aimed to preserve the genetic information. These mechanisms include the action of different DNA polymerases, systems to repair DNA alterations, and various systems of DNA recombination. Among the systems to repair DNA alterations and avoid mutations, we are interested in cellular mechanisms that preserve the genome from mutagenic effect of oxidized bases [GO system], and a postreplicative system named the Mismatch Repair System [MRS] that eliminates some mismatched bases introduced erroneously during the synthesis of DNA. This system also restrains the recombination of divergent DNA sequences. The deficiency of this system in prokaryotes generates “hypermutability”, that is cells with high rates of mutation and recombination. In the last years our laboratory, using P. aeruginosa and E. coli as biological systems, has focused in the functional characterization of the MRS and GO system. We performed genetic and molecular analysis of their components and the phenotypic characterization of cells deficient in these systems, with special emphasis in the relation of mutation rate and mechanisms of antibiotic resistance. We are currently focused on studying the interaction between the various components of the MRS, the replisome and the DNA recombination machinery mediated by RecA. We have designed a genetic device to determine “in vivo”, the rate and molecular characteristics of DNA recombination in different gram-negative species. We also implemented a “fluorescence resonance energy transfer” procedure to analyze “in vitro” the mechanism of recombination catalyzed by different recombinases and the influence of DNA divergence in the recombination reaction.
- Miguel V, Correa IN, Tullio De L, Barra JL, EC Argaraña, Villarreal MA (2013) “Analysis of the interaction interfaces of the N-terminal domain from Pseudomonas aeruginosa MutL” PLoS One Jul 26;8(7):e69907. doi: 10.1371/journal.pone.0069907
- Monti MR*, Morero NR *, Miguel V, EC Argaraña (2013) “nfxB as a Novel Target for Analysis of Mutation Spectra in Pseudomonas aeruginosa” PLoS One, 2013 Jun 7;8(6):e66236. doi: 10.1371/journal.pone.0066236.
- Monti MR*, Miguel V *, Borgogno MV and Argaraña CE (2012) “Functional analysis of the interaction between the mismatch repair protein MutS and the replication processivity factor Beta clamp in Pseudomonas aeruginosa” DNA Repair (Amst) 11:463-469.
- Morero N, Monti RM and Argaraña CE (2011) “Effect of Ciprofloxacin concentration on the frequency and nature of resistant mutants selected from Pseudomonas aeruginosa mutS and mutT hypermutators” Antimicrob Agents Chemother, 55:3668-3676
- Pezza R.J., Villarreal M.A., Montich G.G. and Argaraña C.E. (2002) Vanadate inhibits the ATPase activity and DNA binding capability of bacterial MutS. A structural model for the vanadate-MutS interaction at the Walker A motif. Nucleic Acids Res. 30, 4700-4708.
Researchers members of the group
- Monti, Mariela Roxana. Research Scientist, CONICET
- National Council of Scientific and Technical Research (CONICET). “Molecular analysis of the Mismatch Repair System and its capacity to modulate the genetic recombination in Pseudomonas aeruginosa””, PIP 20130100360.
- Secretary of Science and Technology, Universidad Nacional de Córdoba.
- National Agency of Promotion of Science and Technology (ANPCyT “Study of the genetic recombination and its modulation by the Mismatch Repair System”, PICT 2011, 1797
- 1981. Ph.D., Biological Chemistry. Universidad Nacional de Córdoba. Córdoba, Argentina
- 1975. M.S., Biological Chemistry, School of Chemistry. Universidad Nacional de Córdoba. Córdoba, Argentina
- 2000-present: Professor (2004-present); Associate Professor (2000-2004). Research Scientist; CONICET, since 1987. CIQUIBIC-CONICET. Department of Biological Chemistry, Universidad Nacional de Córdoba, Argentina.
Mutation repair systems in bacteria.
Biochemistry and molecular genetics of components of the Mismatch repair system and the GO system from gram-negative bacteria (P. aeruginosa and E. coli). Production of recombinant proteins. Protein mutagenesis and function. Chromosomal gene disruption. Characterization of various phenotypes caused by disruption of the repair systems. Molecular analysis of homologous recombination in vivo and vitro. Studies on eukaryotic recombinases, in collaboration with Dr. R. Patch (Medical Research Foundation, Oklahoma-USA).
- 1987-2000: Assistant Professor (1987-1994); Associate Professor (1994-2000). Research Scientist; CONICET, since 1987. CIQUIBIC-CONICET. Department of Biological Chemistry, Universidad Nacional de Córdoba, Argentina.
Molecular analysis of human genetic diseases.
Identification of gene mutations and characterization of the phenotypic effects. [Beta Hexosaminidase deficiency; Cystic Fibrosis; Beta-Glucuronidase deficiency; Goucher disease, Glucose-6-phosphatase deficiency, etc ].
Most studies were carried out in collaboration with Dr. R Kremer laboratory, [Center of Studies of Genetics Diseases, Children’s Hospital of Cordoba. Argentina] Some studies were carried out with Dr. Roy Gravel laboratory , [Mc Gill University, Montreal-Canada] and YOU Chou laboratory [National Institutes of Health, Bethesda, MD-USA].
- 1983-1987: Posdoctoral Fellow. Supervisors: Drs Charles R. Cantor and Richard Axel (Nobel Prize of Physiology or Medicine, 2004). Department of Human Genetics. Columbia University, New York. USA.
Cloning of the streptavidin gene and properties of the encoded protein. Amino acid sequencing determination, construction of gene libraries in lambda phage, screening with oligonucleotides, nucleotide sequencing determination. Biochemical, structural and biophysical analysis of the protein.
- 1976-1983: Posdoctoral Fellow, (1981-1983), PhD student (1976-1981). Supervisor: Dr. HS Barra. Department of Biological Chemistry, Universidad Nacional de Córdoba, Argentina.
Posttranslational modification of tubulin. Tyrosination of tubulin in vivo. Partial purification and biochemical characterization of tubulin carboxypeptidase. Detection and analysis of endogenous inhibitors.
Activities described below were carried out in the Department of Biological Chemistry, College of Chemistry Sciences, National University of Córdoba
- Professor of Biotechnology (2003 – present)
- Associate Professor of Biotechnology (1994-2003) and Genetics (2000-2001)
- Assistant Professor of Genetics (1988-1992) and Biotechnology (1993)
- Instructor, Department of Biological Chemistry (1978-1983)
- Guest lecturer: Biological Chemistry, and Biochemistry of Macromolecules courses.
- Curriculum Development.
I was involved in the development and implementation of two courses for the Biochemistry and Licentiate in Chemistry degree: “”Molecular Genetics”” starting in 1988, and “”Biotechnology”” starting in 1993.
Since 2009, I am involved in the development of a Licenciatura (equivalent to a Master degree) in Biotechnology (five-year degree) for the College of Biological Sciences. At present it is in the evaluation process by the National Ministry of Education.
Institutional Management Background
- 2015- Member of the Executive Council of CIQUIBIC.
- 2010-2015. Vice-Director of CIQUIBIC
- 2003-2010. Member of the Executive Council of CIQUIBIC.
- 2002-2004. Director of the Department of Biological Sciences. School of Chemistry, Universidad Nacional de Córdoba
- 1998-2000. Vice-Director of the Department of Biological Sciences. School of Chemistry, Universidad Nacional de Córdoba.
- 1996-1998. Vice-Director of the Department of Biological Sciences. School of Chemistry, Universidad Nacional de Córdoba
Directed Ph.D. Theses
- 2011. Lic. Morero, Natalia “Genetic determinants of resistance to ciprofloxacin in hypermutator strains of P. aeruginosa””
- 2009. Biol. Miguel, Virginia. “The mismatch repair system in bacteria. Structural and functional analysis of the MutS protein””
- 2007. Biol. Filiberti, Adrián “Functional and molecular characterization of proteins with entomopathogenic activity against horn fly (Haematobia irritant)".
- 2005. Lic. Monti, Mariela R. “Biodegradation of 2,4-dinitrotoluene. Generation of recombinant bacteria””
- 2002. Biol. Patch, Roberto J. “Studies of the Mismatch Repair System (MRS) in Pseudomonas aeruginosa. Cloning and characterization of the mutS gene”
- 1995. Lic. Kleiman, Frida E. “Molecular studies of Sandhoff disease. Frequency of mutations in a Argentinean population and studies of irregular structures in the 3´end of the HEXB gene”
- 1995. Biol. Weizetfel, José C. “Characterization of a brain protein structurally related to carboxypeptidase A”
- 1995. Biol. Craving, Andrea M. “Isolation and molecular characterization of p30 cDNA from bovine brain”