- Senior Staff Scientist
- Virol & Micro: Zechiedrich
- Baylor College of Medicine
- Houston, TX, US
- PhD from University of Dundee
- BS from University of Leeds
- Postdoctoral Training at University of California at Santa Barbara
- Postdoctoral Training at Baylor College of Medicine
Throughout my research I have focused on how DNA is able to be an active participant in its transactions. DNA structure, particularly the structure of supercoiled DNA, is much more variable and dynamic than many people realize. This insight has allowed me to contribute to a better understanding of protein-DNA interactions and DNA itself. In the process, I have also developed unique DNA tools that are proving to be extremely useful, not only for basic research, but also clinical applications. I have developed a patented protocol to generate milligram quantities of supercoiled minicircle DNA, as small as 250 bp. Using these DNA minicircles, I 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. Throughout my career I have collaborated with researchers from many disciplines including biochemistry, biophysics, physics, mathematics, structural biology, and medicine.
The development of methods to produce minicircles has proved invaluable for studying the structure of supercoiled DNA, and the enzymes that recognize and manipulate DNA supercoiling. An unexpected discovery was that these minivectors transfect cells with high efficiency and can transfect many clinically relevant cell types that are refractory to transfection with plasmid DNA. We have demonstrated that they hold great promise as a gene therapy tool. Additionally, we developed methods to capture and isolate DNA catenanes, an intermediate in the process to make minicircles. These DNA catenanes provide a means to study another very important reaction catalyzed by topoisomerases, the unlinking of catenated replication products.
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
American Chemical Society (since 2005)
Biochemical Society (since 2008)
Structural Diversity of Supercoiled DNA. Gordon Research Conference. DNA Topoisomerases in Biology and Medicine (2016). Sunday River, Newry, Maine.
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.
- Bizard, A.H. Yang, X. Débat, H. Fogg, J.M. Strick, T.R. Garnier, F. Nadal, M.. "TopA, the Sulfolobus solfataricus topoisomerase III, is a decatenase.." Nucleic Acids Res.. 2018 January 25;46(2):861-872. Pubmed PMID: 29253195
- Wang, Q. Irobalieva R.N. Chiu W., Schmid M.F. Fogg J.M. Zechiedrich L. Pettitt B.M.. "Influence of DNA sequence on the structure of minicircles under torsional stress." Nucleic Acids Res.. 2017 July 27;45(13):7633-7642. Pubmed PMID: 28609782
- Irobalieva, R.N. Fogg J.M. Catanese D.J. Jr. Sutthibutpong, T. Chen M. Barker A.K. Ludtke S.J. Harris S.A. Schmid M.F. Chiu W. Zechiedrich L.. "Structural diversity of supercoiled DNA." Nat Commun.. 2015 October 12;6:8440. Pubmed PMID: 26455586
- Fogg, J.M. Randall, G.L. Pettitt, B.M. Sumners, D.W. Harris, S.A. and Zechiedrich, L... "Bullied no more: when and how DNA shoves proteins around.." Quarterly Review of Biophysics. 2012;45:257-299.
- Catanese D.J. Jr. Fogg J.M. Schrock D.E. 2nd. Gilbert B.E. Zechiedrich L.. "Supercoiled Minivector DNA resists shear forces associated with gene therapy delivery.." Gene Ther.. 2012 January;19(1):94-100. Pubmed PMID: 21633394
- Zhao, N. Fogg, J.M. Zechiedrich L. Yu Z.. "Transfection of shRNA-encoding Minivector DNA of a few hundred base pairs to regulate gene expression in lyphoma cells." Gene Ther.. 2011;18(3):220-224. Pubmed PMID: 20962872
- Fogg J.M. Catanese D.J. Jr. Randall G.L. Swick M.C. Zechiedrich L.. "Differences between positively and negatively supercoiled DNA that topoisomerases may distinguish." Mathematics of DNA Structure, Function and Interactions. 2009;150:73-121.
- Fogg J.M. Kolmakova N. Rees I. Magonov S. Hansma H. Perona J.J. Zechiedrich E.L.. "Exploring writhe in supercoiled minicircle DNA.." J Phys Condens Matter. 2006 March 24;18(14):S145-S159. Pubmed PMID: 19337583
- Hiller D.A. Fogg J.M. Martin A.M. Beechem J.M. Reich N.O. Perona J.J.. "Simultaneous DNA binding and bending by EcoRV endonuclease observed by real-time fluorescence.." Biochemistry. 2003 December 16;42(49):14375-14385. Pubmed PMID: 14661948
- Déclais A.C. Fogg J.M. Freeman A.D. Coste F. Hadden J.M. Phillips S.E. Lilley D.M.J.. "The complex between a four-way DNA junction and T7 endonuclease I.." EMBO J.. 2003 March 17;22(6):1398-1409. Pubmed PMID: 12628932
- Kvaratskhelia M. Wardleworth B.N. Bond C.S. Fogg J.M. Lilley D.M.J. White M.F.. "Holliday junction resolution is modulated by archaeal chromatin components in vitro.." 2002 January 25;277(4):2992-2996. Pubmed PMID: 11709558
- Fogg J.M. Kvaratskhelia, M. White M.F. Lilley D.M.J.. "Distortion of DNA junctions imposed by the binding of resolving enzymes: a fluorescence study.." J. Mol. Biol.. 2001 November 3;313(4):751-764. Pubmed PMID: 11697901
- Fogg D.M.J. Lilley D.M.J.. "Ensuring productive resolution by the junction-resolving enzyme RuvC: large enhancement of the second-strand cleavage rate.." Biochemistry. 2000 December 26;39(51):16125-16134. Pubmed PMID: 11123941
- Fogg J.M. Schofield M.J. Déclais A.C. Lilley D.M.J.. "Yeast resolving enzyme CCE1 makes sequential cleavages in DNA junctions within the lifetime of the complex.." Biochemistry. 2000 April 11;39(14):4082-4089. Pubmed PMID: 10747798
- Fogg J.M. Schofield M.J. White M.F. Lilley D.M.J.. "Sequence and functional-group specificity for cleavage of DNA junctions by RuvC of Escherichia coli.." Biochemistry. 1999 August 31;38(35):11349-11358. Pubmed PMID: 10471285