Greer Professor & Vice Chair for Research, Pathology & Laboratory Medicine
Education & Training
- Psychobiology, UCLA, 1973
- Biology/Biochemistry, UC Santa Barbara, 1975
- Microbiology/Immunology, UCLA, 1980
- UC San Diego, 1980-1982
Areas of Interests
- Research Interest
- Bacterial Pathogenesis and Host-Pathogen Interactions
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. Borrelia burgdorferi (which causes Lyme disease) and Treponema pallidum (the causative agent of syphilis) 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 excellent models for the study of persistent, invasive pathogens. In the case of B. burgdorferi, 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 genes and gene products required for infectivity in a mouse model. Thus far, we have identified and characterized the vls antigenic variation of B. burgdorferi, an elaborate mechanism similar to the Variable Major Protein system of relapsing fever borreliae. In addition, we have determined that the linear plasmids lp25 (and its encoded gene pncA) and lp28-1 are required for full virulence of B. burgdorferi during infection in mice. We are currently taking a global approach to identify additional genes encoding virulence determinants important in the pathogenesis of Lyme disease, as well as genes required for vls recombination and immune evasion. Little is known about T. pallidum due to the inability to culture the organism continuously in vitro. In collaboration with Dr. George Weinstock and the Institute of Genomic Research in Rockville, Md., the complete sequence analysis of the 1.14 megabase chromosome of T. pallidum was completed in 1998; the genome sequences of several related subspecies and strains have also been determined using second generation sequencing approaches. The sequence of the 2.84 megabase genome of Treponema denticola, an oral spirochete involved in periodontal disease, was published in April 2004. We are currently applying ‘functional genomics’ to the elucidation metabolism, structure, and pathogenic mechanisms of these spirochetes. In addition, 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 to elucidate the architecture of the flagellar motor and other structural elements of these organisms.
Selected Publications (see PubMed link for complete listing)
- 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
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-.