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Molecular Virology and Microbiology

Houston, Texas

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Department of Molecular Virology and Microbiology
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Lynn Zechiedrich, Ph.D.

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Lynn Zechiedrich, Ph.D.

Professor
Department of Molecular Virology & Microbiology

Research Interests

Fluoroquinolone Resistance in E. coli

Fluoroquinolones are among the most potent, widely prescribed, broad-spectrum oral antibiotics. Quinolones kill bacteria by targeting the two type-2 topoisomerases, gyrase and topoisomerase IV. These essential enzymes pass DNA strands through each other and are required for DNA replication, recombination, transcription, chromosome segregation, and maintenance of DNA supercoiling levels. Quinolones stabilize the normal, transient topoisomerase-DNA cleavage intermediate. With a mechanism that is not well understood, processes such as replication and transcription affect the drug-stabilized topoisomerase-DNA adducts to cause cell death.

To reach their cellular targets, drugs must first penetrate the defense system of the bacterial cell. Not only are cells well-equipped to withstand treatment with drugs, but bacteria undergo genetic alteration to become resistant to drugs. Although drug resistant bacteria are one of the most critical problems facing the medical community today, huge gaps remain in our knowledge of how cells resist drugs. Therefore, the goal of our research is to determine how the model system Escherichia coli respond to and resist treatment with the quinolone antibiotics. Ultimately, our results may be used to design better chemotherapeutics to help prevent the worldwide problem of drug resistance.

DNA Topoisomerases, DNA Structure and DNA Topology

By passing DNA strands through each other, the ubiquitous topoisomerases control chromosome condensation, chromosome segregation, DNA replication, DNA transcription, and DNA recombination. Topoisomerases break and reseal DNA to modulate DNA supercoils, DNA catenanes, and DNA knots. Topoisomerases are the cellular targets for widely prescribed anticancer and antibiotic agents. The normally short-lived, broken DNA intermediate produced by topoisomerases is increased by the drugs, which causes cell death. We use biochemical, biophysical and genetic techniques to determine how topoisomerases carry out the cellular roles and how drugs block their function. We also study DNA structure and have utilized the topoisomerases to create new gene therapy vectors.

Human Gene Therapy

During our research into DNA structure and topology, our group has developed a new class of minimized circular DNA vectors called Minivector DNA. Minivector DNAs can be ordered at Twister Biotech. Containing only a promoter and open reading frame, these DNA vectors are devoid of the large size and bacterial sequences that hamper plasmid DNA as a viable non-viral gene therapy vector. We synthesize milligram quantities of Minivector DNA as small as 200 bp, and have transfected a variety of difficult human cell lines, including suspension lymphoma cells. Currently, we are exploring the use of Minivector DNA as an expression vector for gene replacement in cell culture and animal models for human genetic diseases.

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Contact Information

Department of Molecular Virology & Microbiology
Baylor College of Medicine
One Baylor Plaza, MS BCM385
Houston, TX, 77030, U.S.A.

713-798-5126
elz@bcm.edu

Education

Ph.D. - Vanderbilt University
Postdoctoral - University of California, Berkeley

Awards, Appointments and Honors

July 2010 - June 2013 Human Frontier Science Program Award
February 2009 - 2nd place prize, Applied Biosystems SOLiDTM 3 System $10K Genome Grant Program
May 2008 - May 2011 Advisory Committee, Burroughs Wellcome Fund Institutional Program, Unifying Population and Laboratory-based Sciences
August 2007 - Finalist, NIH Director's Pioneer Award
January 2004 - December 2004 Burroughs Wellcome Fund Award
July 1998 - June 2002 Burroughs Wellcome Fund New Investigator Award in the Toxicological Sciences
March 1998 - March 1999 Curtis Hankamer Research Award (BCM)
October 1997 - Fellowship from Juan March Institute, Madrid, Spain, to attend International workshop

Zechiedrich's Lab Web Site

Google Scholar

Recent Publications (PubMed)

Students

Kimberly M. Carlson
Erol Bakkalbasi
Truston J. Bodine
Michael A. Evangelista

PostDoctoral Fellows

Daniel J. Catanese, Jr., Ph.D.
Jonathan M. Fogg, Ph.D.
Milenka Arevalo-Soliz, Ph.D.