个人简介

Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease Genomics Proteomics and Bioinformatics

Lyme borreliosis (Lyme disease) is the most common vector transmitted disease in the northern hemisphere. It is caused by the spirochete Borrelia burgdorferi and other Borrelia species. The disease is typically transmitted from infected mice to humans by a bite from an infected tick. If not properly diagnosed and treated, Lyme disease can be severely debilitating and may result in arthritis, neurological symptoms, heart abnormalities and a variety of other problems. Global warming is promoting the expansion of areas where infected ticks and Lyme borreliosis is found. Borrelia burgdorferi is a fascinating organism with a variety of intriguing features. Our studies focus on several aspects of the biology of Borrelia burgdorferi: 1) Antigenic variation – By constantly changing the sequence of a surface-bound liopoprotein, VlsE, B. burgdorferi can stay one step of the host immune system and outrun the acquired immune response. This escape in immune-surveillance results in persistent infection of the host. The antigenic variation process is driven by gene conversion events at the vlsE locus, molecular details governing antigenic variation remain unknown and are under investigation in the lab. 2) Global gene regulation by the HrpA helicase – Global gene regulation is an important feature in the B. burgdorferi life cycle. The expression of about 150 genes is regulated as the spirochete transitions from the tick vector to the vertebrate host. We have shown that one of the global regulatory pathways involves the HrpA RNA helicase. Infection cannot occur in the absence of HrpA. Moreover, while many bacteria have multiple RNA helicases, B. burgdorferi encodes only the HrpA RNA helicase, making Borrelia a good model system for functional studies on HrpA. 3) B. burgdorferi dissemination – Lyme spirochetes can enter the host vasculature and ride for free throughout the body, exiting at diverse locations to cause a variety of problems. The process of dissemination is complex and poorly understood. In collaboration with the labs of Jenifer Coburn (Medical College of Wisconsin) and John Leong (Tufts University) we are studying this important problem. Our intravital microscopic analysis has revealed important new information and is the first high resolution imaging of spirochetes at work in a living mammalian host (see video links). We use a wide variety of methodologies to study the above problems, including genomics, proteomics, molecular biology, genetics, next generation sequencing, nucleic acid biochemistry, protein biochemistry, structural biology and intravital microscopy.

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Kobryn K, Chaconas G. (2014) Hairpin telomere resolvases. Microbiology Spectrum 2(6):MDNA3-0023-2014. doi:10.1128/microbiolspec.MDNA3-0023-2014. Mobile DNA III, in press. Lee, W.-Y., Sanz, M.-J., Wong, C.H.Y., Hardy, P.-O. Salman-Dilgimen, A., Moriarty, T.J., Chaconas, G. Marques, A. Krawetz, R., Mody, C.H. and Kubes, P. (2014) Visualizing iNKT cells in joints: an extravascular cytotoxic barrier for invading Lyme Borrelia. PNAS, 111, 13936-13941. Bandy NJ, Salman-Dilgimen A, Chaconas G. Construction and Characterization of a Borrelia burgdorferi Strain with Conditional Expression of the Essential Telomere Resolvase, ResT. J Bacteriol. 2014 Jul 1;196(13):2396-2404 Salman-Dilgimen A, Hardy PO, Radolf JD, Caimano MJ, Chaconas G. HrpA, an RNA helicase involved in RNA processing, is required for mouse infectivity and tick transmission of the Lyme disease spirochete. PLoS Pathog. 2013 Dec;9(12):e1003841. Coburn J, Leong J, Chaconas G. Illuminating the roles of the Borrelia burgdorferi adhesins. Trends Microbiol. 2013 Aug;21(8):372-9. Chaconas G, Norris SJ. Peaceful coexistence amongst Borrelia plasmids: Getting by with a little help from their friends? Plasmid. 2013 Sep;70(2):161-7. Hardy PO, Chaconas G. The Nucleotide Excision Repair System of Borrelia burgdorferi Is the Sole Pathway Involved in Repair of DNA Damage by UV Light. J Bacteriol. 2013 May;195(10):2220-31. Walia R, Chaconas G. Suggested role for G4 DNA in recombinational switching at the antigenic variation locus of the Lyme disease spirochete. PLoS One. 2013;8(2):e57792. Lin T, Gao L, Zhang C, Odeh E, Jacobs MB, Coutte L, Chaconas G, Philipp MT, Norris SJ. Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity. PLoS One. 2012;7(10):e47532 Moriarty TJ, Shi M, Lin YP, Ebady R, Zhou H, Odisho T, Hardy PO, Salman-Dilgimen A, Wu J, Weening EH, Skare JT, Kubes P, Leong J, Chaconas G. Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules.Mol Microbiol. 2012 Dec;86(5):1116-31 Chaconas G. CSM murray award lecture - functional studies of the Lyme disease spirochete - from molecules to mice. Can J Microbiol. 2012 Mar;58(3):236-48. Salman-Dilgimen A, Hardy PO, Dresser AR, Chaconas G. HrpA, a DEAH-box RNA helicase, is involved in global gene regulation in the Lyme disease spirochete. PLoS One. 2011;6(7):e22168. Chaconas G, Kobryn K. Structure, Function, and Evolution of Linear Replicons in Borrelia. Annu Rev Microbiol, ;64:185-202, 2010 Lee WY, Moriarty TJ, Wong CH, Zhou H, Strieter RM, van Rooijen N, Chaconas G, Kubes P. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol 11(4):295-302, 2010 Dresser AR, Hardy PO, Chaconas G. Investigation of the Genes Involved in Antigenic Switching at the vlsE Locus in Borrelia burgdorferi: An Essential Role for the RuvAB Branch Migrase. PLoS 5(12):e1000680, 2009 Chaconas, G. (2008), "Replication of linear plasmids in bacteria", in Clewell, D. (ed.), Biology and Significance of Plasmids: A multi-talk discussion of extrachromosomal elements in microorganisms, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://www.hstalks.com/?t=BL0461651-Chaconas) Lefas G, Chaconas G. High-Throughput Screening identifies Three Inhibitor Classes of the Telomere Resolvase from the Lyme Disease Spirochete. Antimicrob Agents Chemother 53(10):4441-9, 2009 Moriarty TJ, Chaconas G. Identification of the Determinant Conferring Permissive Substrate Usage in the Telomere Resolvase, ResT. J Biol Chem 284(35): 23293-301, 2009 Tourand Y, Deneke J, Moriarty TJ, Chaconas G. Characterization and in vitro reaction properties of 19 unique hairpin telomeres from the linear plasmids of the lyme disease spirochete. J Biol Chem 284(11): 7264-72, 2009 Norman MU, Moriarty TJ, Dresser AR, Millen B, Kubes P, Chaconas G. Molecular mechanisms involved in vascular interactions of the lyme disease pathogen in a living host. PLoS Pathog 4(10): e1000169, 2008 Moriarty TJ, Norman MU, Colarusso P, Bankhead T, Kubes P, Chaconas G. Real-time high resolution 3D imaging of the lyme disease spirochete adhering to and escaping from the vasculature of a living host. PLoS Pathol 4(6): e1000090, 2008 Deneke J and Chaconas G. Purification and properties of the plasmic maintenance proteins from the Borrelia burgdorferi linear plasmid lp17. J Bacteriol 190(11): 3992-4000, 2008