`Yuri Voziyanov. Gene editing. Genome Engineering. Flp - FRT, Cre - loxP, TD - TDRT, R - R1RT site-specific DNA recombination
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The Jackson Laboratory



Yuri Voziyanov
Professor of Biology

Marvin T. Green, Sr.
Endowed Professor
in Pre-medicine

Louisiana Tech University
School of Biological Sciences / Institute for Micromanufacturing
Carson-Taylor Hall 121
1 Adams Blvd.
Ruston, LA 71272

318.257.2694
voziyan@latech.edu

1991 - BS/MS, Kiev State University, Kiev, Ukraine
1996 - Ph.D., Institute of Molecular Biology and Genetics, Kiev, Ukraine
1997 - 2003 - Postdoctoral training, University of Texas at Austin and European Molecular Biology Laboratory, Heidelberg, Germany



RESEARCH

There are three directions of our current research: gene editing/genome engineering, protein engineering, and aging.

Gene editing/genome engineering

The main direction of our research is correction of genetic defects. Currently, we are working on fixing the mutations that cause sickle cell anemia. In our experiments we use several gene editing/genome engineering tools: target-specific variants of the tyrosine DNA recombinases Flp and Cre (as well as related recombinases) along with the CRISPR/Cas9 and TALEN systems.

Site-specific recombinases of the tyrosine type can bring about a full range of the DNA rearrangement reactions: integration and excision, inversion, translocation, and cassette replacement. Tyrosine recombinases mediate these reactions from start to finish in any cell type, without any dependence on the cell DNA repair machinery; they are thus particularly useful for controlled genome rearrangements.

For our gene editing/genome engineering experiments, we design non-viral vectors with different functional elements, including S/MAR and insulator elements. We also experiment with in vitro transcribed mRNA, shRNA, transposase-mediated integrating vectors, and minicircles.

Protein engineering

Our second research direction is protein engineering. We evolve variants of tyrosine recombinases with new target specificity and analyze how individual amino acid substitutions influence the specificity switch. In this research we use Flp, Cre, TD, and R recombinases.

Tyrosine recombinase family is huge and comprised of over 1000 members that have similar 3D fold but remarkably different target specificity. These properties make tyrosine recombinases an attractive model for modifying enzyme specificity and deciphering the functional role of their amino acid residues in target recognition. .

Aging

The third emerging direction of our research is aging. We want to understand how to systemically eliminate harmful modifications that cells acquire during the aging process and to bring cells to their default state thus rejuvenating them. As a model organism, we use budding yeast as they are able to reset their lifespan during spore formation.



PUBLICATIONS (PubMed database)

SELECTED PUBLICATIONS


  • Voziyanova E., Li F., Shah R., Voziyanov Y.
    Genome targeting by hybrid Flp-TAL recombinases.
    Scientific Reports, 2020

  • Voziyanova E., Anderson R.P., Voziyanov Y.
    Dual Recombinase-Mediated Cassette Exchange by Tyrosine Site-Specific Recombinases.
    Methods Mol. Biol., 2017

  • Voziyanova E., Anderson R.P., Shah R., Li F., Voziyanov Y.
    Efficient genome manipulation by variants of site-specific recombinases R and TD.
    J. Mol. Biol., 2016

  • Shah R., Li F., Voziyanova E., Voziyanov Y.
    Target-specific variants of Flp recombinase mediate genome engineering reactions in mammalian cells.
    FEBS J., 2015

  • Voziyanova E., Malchin N., Anderson R.P., Yagil E., Kolot M., Voziyanov Y.
    Efficient Flp-Int HK022 dual RMCE in mammalian cells.
    Nucleic Acids Res., 2013

  • Anderson R.P., Voziyanova E., Voziyanov Y.
    Flp and Cre expressed from Flp-2A-Cre and Flp-IRES-Cre transcription units mediate the highest level of dual recombinase-mediated cassette exchange.
    Nucleic Acids Res., 2012

  • Shultz J.L., Voziyanova E., Konieczka J.H., Voziyanov Y.
    A genome-wide analysis of FRT-like sequences in the human genome.
    PLoS One, 2011

  • Malchin N., Molotsky T., Borovok I., Voziyanov Y., Kotlyar A.B., Yagil E., Kolot M.
    High efficiency of a sequential recombinase-mediated cassette exchange reaction in Escherichia coli.
    J. Mol. Microbiol. Biotechnol., 2010