Education

BA
Psychobiology, UCLA, 1973
MS
Biology/Biochemistry, UC Santa Barbara, 1975
PhD
Microbiology/Immunology, UCLA, 1980
Postdoctoral
UC San Diego, 1980-1982

Areas of Interests

Research Interests

Bacterial Pathogenesis and Host-Pathogen Interactions

Research Information

Bacterial Pathogenesis and Host-Pathogen Interactions

Our research is driven by an interest in bacterial pathogenesis and its relationship with microbial physiology, structure, and genetics. Treponema pallidum (the causative agent of syphilis) and Borrelia burgdorferi (which causes Lyme disease) are spirochetes that cause chronic, multisystemic diseases.  These organisms can invade almost any tissue and survive and cause disease in the host for years to decades, and thus serve as important examples of persistent, invasive pathogens.

Long-term in vitro culture of Treponema pallidum

The culture of T. pallidum in vitro has been a research goal ever since its identification as the cause of syphilis in 1905. Our group recently described a system that supports the long-term multiplication of T. pallidum in a tissue culture system (Edmondson et al., 2018). We have now maintained exponential growth of T. pallidum for over a year and have embarked on an NIH-funded project to 1) optimize the tissue culture system, 2) delineate nutritional requirements and growth characteristics, with the goal of developing an axenic (cell-free) culture system, and 3) investigate the possibility of mutational analysis of T. pallidum. Other potential applications include the direct culture of T. pallidum from patient specimens and the use of this system for antimicrobial susceptibility testing.

Molecular genetics of Lyme disease pathogenesis

Molecular genetic techniques such as transposon mutagenesis (including signature tagged mutagenesis), PCR, Luminex®-based high-throughput screening procedures, and reverse genomics are being utilized in combination with infectivity studies to identify B. burgdorferi genes and gene products required for infectivity in a mouse model. Using such approaches, our group identified and characterized the vls antigenic variation system of B. burgdorferi, an elaborate mechanism similar to the Variable Major Protein system of relapsing fever borreliae. We have also utilized a global approach to identify additional genes encoding virulence determinants important in the pathogenesis of Lyme disease through the screening of a transposon mutant library using high-throughput approaches (including Tn-seq).

Ultrastructure of pathogenic spirochetes

Cryo-electron tomography, a relatively new electron microscopy technique that creates 3D images of bacteria, is being utilized in collaborative studies with Dr. Jun Liu at Yale University to elucidate the architecture of the flagellar motor and other structural elements of these organisms.

Publications

Publication Information

Selected Publications (see Influuent link for complete listing)

  • Norris SJ. 2018. Catching up with Lyme disease antigenic variation computationally. (Commentary) Trends Microbiol. 26(8):644-645. doi: 10.1016/j.tim.2018.05.017. PMID: 29903419. Link
  • Edmondson, DG, Hu B, Norris SJ. 2018. Long-term in vitro culture of the syphilis spirochete, Treponema pallidum. MBio. 9(3). pii: e01153-18. doi: 10.1128/mBio.01153-18. PMID: 29946052 Link
  • Arora N, J Verena, GJ Schuenemann, A Peltzer, A Seitz, A Herbig, M Strouhal, L Grillová, L Sánchez-Busó, D Kühnert, KI. Bos, N Juricevic, L R Davis, L Paštěková, S Bruisten, P Komericki, P French, P Grant, MA Pando, LG Vaulet, M R Fermepin, A Martinez, A Centurion Lara, L Giacani, SJ Norris, D Smâjs, PP Bosshard, F González-Candelas, K Nieselt, J Krause and HC Bagheri. 2016. Origin of modern syphilis and emergence of a pandemic cluster. Nature Microbiology 5;2:16245. doi: 10.1038/nmicrobiol.2016.245. PMID: 27918528
  • Edmondson DG, Prabhakaran S, Norris SJ, Ullmann AJ, Piesman J, Dolan M, Probst C, Radzimski C, Stöcker W, Komorowski L. Enhanced protective immunogenicity of homodimeric Borrelia burgdorferi Outer Surface Protein C.  Clin Vaccine Immunol. 2016 Oct 12. pii: CVI.00306-16. PMCID: PMC5216437
  • Bourret TJ, Lawrence KA, Shaw JA, Lin T, Norris SJ, Gherardini FC.  2016.  The nucleotide excision repair pathway protects Borrelia burgdorferi from nitrosative stress in Ixodes scapularis ticks.  Front Microbiol. 2016 Sep 7;7:1397. doi: 10.3389/fmicb.2016.01397.  PMCID: PMC5013056
  • Troy EB, Lin T, Gao L, Lazinski DW, Lundt M, Camilli A, Norris SJ, Hu LT. Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi. Mol Microbiol. 2016 Sep;101(6):1003-23. doi: 10.1111/mmi.13437. PMCID: PMC5028225
  • Chu, C-Y, PE Stewart, A Bestor, B Hanson, T Lin, L Gao, SJ Norris, and PA Rosa. 2016. Function of the Borrelia burgdorferi FtsH homolog is essential for viability both in vitro and in vivo, and independent of HflK/C. mBio 7(2). pii: e00404-16. doi: 10.1128/mBio.00404-16. PMC4850261
  • Khajanchi, BK, E Odeh, L Gao, M Jacobs, MT Philipp, T Lin, and SJ Norris. 2016. Phosphoenolpyruvate phosphotransferase system components modulate gene transcription and virulence of Borrelia burgdorferi.  Infect Immun 84:754 –764. doi:10.1128/IAI.00917-15. PMC4771366
  • Lin, T., L. Gao, X. Zhao, J. Liu, and S. J. Norris.  2015.  Mutations in the Borrelia burgdorferi flagellar type III secretion system genes fliH and fliI profoundly affect spirochete flagellar assembly, morphology, motility, structure and cell division.  mBio 6(3):e00579-15. doi:10.1128/mBio.00579-15, PMC4436065.
  • Čejková, D. M. Strouhal, S.J. Norris, G. M. Weinstock and D.Šmajs.  2015.  A retrospective study on genetic heterogeneity within Treponema Strains: Subpopulations are genetically distinct in a limited number of positions.  PLoS Negl Trop Dis. 2015 Oct 5;9(10):e0004110. doi: 10.1371/journal.pntd.0004110.  PMID: 26436423.
  • Darkoh, C., H. L. DuPont, S. J. Norris, and H. B. Kaplan.  2015.  Toxin synthesis by Clostridium difficile is stringently regulated through a quorum signaling mechanism.  mBio 6(2):e02569-14. doi:10.1128/mBio.02569-14, PMC4453554.
  • Norris SJ. 2014. vls antigenic variation systems of Lyme disease Borrelia: eluding host immunity through both random, segmental gene conversion and framework heterogeneity. Microbiol Spectrum 2(6):MDNA3-0038-2014. doi:10.1128/microbiolspec. MDNA3-0038-2014, PMC4480602.
  • Lin T, Troy EB, Hu LT, Gao L, Norris SJ. 2014. Transposon mutagenesis as an approach to improved understanding of Borrelia pathogenesis and biology. Front Cell Infect Microbiol 4: 63.  Abstract
  • Zhao X, Norris SJ, Liu J.  2014.  Molecular architecture of the bacterial flagellar motor in cells. Biochemistry. 53:4323-4333.  PMID: 24697492  Abstract
  • Zhao X, Zhang K, Boquoi T, Hu B, Motaleb MA, Miller KA, James ME, Charon NW, Manson MD, Norris SJ, Li C, Liu J. 2013. Cryoelectron tomography reveals the sequential assembly of bacterial flagella in Borrelia burgdorferi. Proc Natl Acad Sci (USA) 110: 14390-14395. Abstract
  • Chaconas G, Norris SJ. 2013. Peaceful coexistence amongst Borrelia plasmids: Getting by with a little help from their friends? Plasmid 70: 161-167.  Abstract
  • Troy EB, Lin T, Gao L, Lazinski DW, Camilli A, Norris SJ, Hu LT. 2013. Understanding barriers to Borrelia burgdorferi dissemination during infection using massively parallel sequencing. Infect Immun 81: 2347-2357.  Abstract
  • Lin T, Gao L, Zhang C, Odeh E, Jacobs MB, Coutte Lc, Chaconas G, Philipp MT, Norris SJ. 2012. Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: Insights into the genes required for mouse infectivity. PLoS ONE 7: e47532. Abstract
  • Norris, S J., J. A. Howell, E. A. Odeh, T. Lin, L. Gao, and D. G. Edmondson. 2011.  High-throughput plasmid content analysis of Borrelia burgdorferi B31 using Luminex multiplex technology.  Appl. Env. Microbiol. 77:1483-1492. Abstract

Additional Information

Academic Appointments

Univ. of California at San Diego School of Medicine, Department of Pathology
  • Assistant Research Pathologist,  1981‑1982.
UTHealth Medical School, Dept. of Pathology and Laboratory Medicine
  • Assistant Professor, 1982‑1989.
  • Associate Professor, 1989-1996.
  • Cross Appointment, Dept. of Microbiology and Molecular Genetics , 1990-.
  • Professor, 1996-.
  • Vice Chair for Research, 1998-.
  • Robert Greer Professor of Biomedical Sciences, 2003-.

Honors and Awards

  • Fellow, American Academy of Microbiology, 1993-.
  • Faculty Mentor of the Year, University of Texas Medical School, 2000.
  • Karin Ippen-Ihler Lectureship, Texas A&M University,  2003.
  • Chancellor’s Entrepreneurship and Innovation Award for Multiple Institution Projects, University of Texas System, 2007.
  • Regents Outstanding Teacher Award, University of Texas Health Science Centers, 2013.
  • Member, The University of Texas Kenneth I. Shine Academy of Health Science Education, 2014-.

Other Professional Activities

  • Reviewer, National Institutes of Health, Institute of Allergy and Infectious Diseases (over 40 study sections and 18 teleconference review panels)
  • Regular Member, Bacteriology and Mycology I Study Section, 1999-2003
  • Chair, Infectious Diseases & Microbiology-B Special Emphasis Panel for R21 and R03 applications: June 2014, October 2014, October 2015.
  • Vice Chair and Chair, Gordon Research Conference on Biology of Spirochetes, 1996-2000.
  • Member, Board of Editors, mBio, 2013-.
  • Member, Editorial Board, Infection and Immunity, 1994-.

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