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Zechiedrich Laboratory

Houston, Texas

Supercoils in architecture echo the structure of DNA.
Zechiedrich Lab
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Jonathan M. Fogg, Ph.D.

Photo Jonathan M. Fogg, Ph.D.

Senior Staff Scientist
Jan 2012 - present

Postdoctoral Fellow
May 2005 - Dec 2011
Department of Molecular Virology & Microbiology

Phone: 713-798-6248
Fax: 713-798-7375

Supercoiled DNA Minicircles for probing DNA structure, DNA topoisomerases and as a vector for gene therapy (Minivectors)

I have developed a patented protocol to generate milligram quantities of supercoiled minicircle DNA, as small as 250 bp. Using these DNA minicircles I am able to precisely determine the supercoiling dependence of topoisomerase binding and additionally elucidate the mechanism through which DNA topoisomerases recognize their supercoiled DNA substrate and determine where to act. These minicircles also provide a unique insight into the structure of supercoiled DNA, including previously unappreciated differences between overwound and underwound DNA.

In addition, I have been exploring the possibility of using supercoiled minicircles as a vector for gene therapy. Minivectors are transfected with much higher efficiency than larger plasmid vectors, are resistant to shear forces and nucleases encountered during delivery and are able to mediate gene knockdown. Based on these findings Minivector DNA holds great promise as a new gene therapy tool. Potential therapeutic applications of Minivectors are currently being tested in collaboration with colleagues at Baylor College of Medicine.

Funding
Program in Mathematics and Molecular Biology
Awards

Poster Prize, 11th Structural Biology Symposium (2006), Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas

1st Place, Poster Prize, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Annual Retreat (2005), Baylor College of Medicine, Houston, Texas

Professional Societies

American Chemical Society (since 2005)
Biochemical Society (since 2008)

Publications

Bullied no more: when and how DNA shoves proteins around. Fogg, J.M.; Randall, G.L.;Pettitt, B.M.;Sumners, D.W.; Harris, S.A.; and Zechiedrich, L.. Quarterly Review of Biophysics, in press.

Supercoiled Minivector DNA resists shear forces associated with gene therapy delivery. Catanese, D.J. Jr., Fogg, J.M., Schrock, D.E.II, Gilbert B.E. and Zechiedrich, L. Gene Therapy. (2011) 19:94-100.

Transfection of shRNA-encoding Minivector DNA of a few hundred bp to regulate gene expression in lymphoma cells. Zhao, N., Fogg, J.M., Zechiedrich, L., and Zu, Y. Gene Therapy. 18 (2011), 220-224.

Differences between positively and negatively supercoiled DNA that topoisomerases might distinguish. Fogg, J.M., Catanese D.J. Jr., Randall, G.L., Swick, M.C., and Zechiedrich, L. Proc. Institute Math. App. 150 (2009), 73- 121.

Exploring writhe in supercoiled minicircle DNA. Jonathan M. Fogg, Natalia Kolmakova, Ian Rees, Sergei Magonov, Helen Hansma, John J. Perona and E. Lynn Zechiedrich. J. Phys.: Condens. Matter 18 (2006) S145-S159.

Simultaneous DNA binding and bending by EcoRV endonuclease observed by real-time fluorescence. Hiller DA, Fogg JM, Martin AM, Beechem JM, Reich NO, and Perona JJ. Biochemistry. 42 (2003) 14375-14385.

The complex between a four-way DNA junction and T7 endonuclease I. Declais AC, Fogg JM, Freeman AD, Coste F, Hadden JM, Phillips SE, and Lilley DM. EMBO J. 22 (2003) 1398-1409.

Holliday junction resolution is modulated by archaeal chromatin components in vitro. Kvaratskhelia M, Wardleworth BN, Bond CS, Fogg JM, Lilley DM, and White MF. J Biol Chem. 277 (2002) 2992-2996.

Distortion of DNA junctions imposed by the binding of resolving enzymes: a fluorescence study. Fogg JM, Kvaratskhelia M, White MF, and Lilley DM. J Mol Biol. 313 (2001) 751-764.

Ensuring productive resolution by the junction-resolving enzyme RuvC: large enhancement of the second-strand cleavage rate. Fogg JM and Lilley DM. Biochemistry. 39 (2000) 16125-16134.

Yeast resolving enzyme CCE1 makes sequential cleavages in DNA junctions within the lifetime of the complex. Fogg JM, Schofield MJ, Declais AC, and Lilley DM. Biochemistry. 39 (2000) 4082-4089.

Sequence and functional-group specificity for cleavage of DNA junctions by RuvC of Escherichia coli. Fogg JM, Schofield MJ, White MF, Lilley DM. Biochemistry. 38 (1999) 11349-11358.


Invited Talks

Supercoiling in DNA minicircles: To get the big picture, think small. Banff International Research Station workshop 10w5100: Mathematics and physics of polymer entanglement (2010). The Banff Centre, Banff, Canada.

Dissecting the supercoiling dependence of topoisomerases using minicircle DNA. Topo2008: DNA Topoisomerases in Biology and Medicine (2008). John Innes Centre, Norwich, UK.

Supercoiled minicircle DNA as a probe of DNA structure and enzyme-DNA interactions. American Chemical Society southwest regional meeting (2006), Houston, Texas.

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