Areas of Interests

Research Interests

Bacterial pathogenesis, Host-Pathogen Interactions, Bacteria genetics, Functional genomics, Pathogenomics, Metagenomics, Emerging and
Re-Emerging Infectious diseases

Research Information

Identification of the virulence determinants using Signature-Tagged Mutagenesis system in combination with Luminex®-based high-throughput technology, and infectivity studies in mouse and tick models.

We use the spirochete Borrelia burgdorferi (Bb), the causative agent of Lyme disease (LD), as a model bacterium to study the fundamental aspects of bacteria pathogenesis and its relationship with microbial physiology, structure, and genetics. The highly invasive spirochete is an obligate parasite in both ticks and mammals and produces no known toxins, but is able to colonize, disseminate, and invade almost any tissue from humans and animals, establish persistent infection for months to years in the presence of an active immune response, induce inflammatory responses and tissue damage, and thus serve as a models for the study of persistent infection of invasive bacteria. Little is known about the mechanisms of pathogenesis of LD. We ask the question what genes in the Bb genome are responsible for the pathogenesis and long-term survival, and how can these genes be identified? Our strategy is to analyze the Bb virulence determinants by Signature-Tagged Mutagenesis in combination with high-throughput Luminex® FlexMapTM technology, and infectivity studies to identify genes and gene products required for infectivity in a mouse model. Thus far, we have constructed a high density, sequence defined transposon library. The insertion sites of 4,480 transposon mutants have been determined. More than 800 genes in chromosome and plasmids have been inactivated, the infectivity of these mutants has been determined.

Elucidation of the function, metabolism, structure, and pathogenic mechanisms of virulence determinants based on their functional categories.

We are currently applying ‘functional genomics and pathogenomics’ to elucidate the function, metabolism, structure, and pathogenic mechanisms of Bb based on their functional categories. Transposon mutations in genes associated with DNA recombination and repair, chemotaxis, motility, the PEP-PTS, other transport systems, plasmid maintenance, gene regulation, sRNA genes, carbohydrate, amino acid, and nucleic acid and other important metabolic pathways, predicted lipoproteins, conserved hypothetical proteins, hypothetical proteins, protease, and complement regulator-acquiring surface proteins (CRASPs) of Bb were selected for STM screening. A representative number of mutants in intergenic regions were also tested for infectivity to evaluate potential polar effects, small RNA genes, and regulatory regions. The result of this study will be a comprehensive view of the Bb genes required for mammal-tick infectious cycle, and will fuel the detailed analysis of the functional roles of these genes in future years.

Roles of DNA repair and recombination proteins in vlsE recombination.

We characterized the mutations in 23 genes involved in DNA recombination and repair, the results indicated that transposon mutants in ruvA, ruvB, and mutS exhibited reduced infectivity in mice and greatly diminished vlsE recombination. RuvA, RuvB, and MutS are the first trans-acting factors identified as necessary for vlsE recombination and antigenic variation.

Structure and function of Borrelia burgdorferi Flagellar Type III Secretion System.

fliH, fliI, and flbA transposon mutants were utilized to dissect the mechanism of the Borrelia type III secretion system. Mutations in the B. burgdorferi flagellar type III secretion system genes fliH, fliI, and flbA profoundly affect spirochete flagellar assembly, morphology, motility, structure, and cell Division.

Role of carbon availability in environmental adaptation by Borrelia burgdorferi

Transposon mutagenesis coupled with massively parallel sequencing (Tn-seq) are used to better understand how this organism is able to respond to its environment by sensing the nutrients that are available.

CRASP-mediated Serum Resistance by Borrelia burgdorferi

A targeted, erp Tn- and deletion mutants will be tested if it displays defects in FH/CFHR binding, complement activation in vitro, and bacteremia and tissue colonization in the murine model.

Unraveling the Mystery of Southern Tick-Associated Rash Illness (STARI) in Texas

Illnesses consistent with Lyme disease have been reported in Texas and the south central U.S. Because the causative agent has not been isolated from patients, the term “Southern Tick-Associated Rash Illness” (STARI) was recently introduced by the CDC to describe this syndrome. To date no one has been able to identify, characterize, or culture organisms associated with STARI. We apply different approaches to the identification of organisms associated with STARI. We believe that this approach will significantly advance our understanding of STARI, and, more generally, the biology of tick-transmitted diseases and provide avenues for the systematic diagnosis, treatment, and prevention of this disease.

Publications

Publication Information

  • Ramsey E. Meghan, Jenny A. Hyde, Diana N. Medina, Tao Lin, Lihui Gao, Maureen E. Lundt, Xin Li, Steven J. Norris, Jon T. Skare, Hu T. Linden. 2017. A high-throughput genetic screen identifies previously uncharacterized Borrelia burgdorferi genes important for resistance against reactive oxygen and nitrogen species. PLoS Pathog. 13(2): e1006225. doi:10.1371/journal.ppat.1006225. PMID: 28212410.
  • 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. 2016. 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:e00579-15. PubMed
  • 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.  PubMed
  • 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.  PubMed
  • Lin T, L Gao, C Zhang, E Odeh, MB Jacobs, L Coutte, G Chaconas, MT Philipp, SJ Norris. 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 PubMed
  • Norris, SJ, T Lin. 2011. Out of the woods: the remarkable genomes of the genus Borrelia. J Bacteriol. 193(24): 6812-4. doi: 10.1128/JB.06317-11 PubMed
  • Norris, SJ., J A Howell, E.A Odeh, T Lin, L Gao, and DG Edmondson. 2011. High-throughput plasmid content analysis of Borrelia burgdorferi B31 using Luminex multiplex technology. Appl. Env. Microbiol. 77:1483-1492. PubMed
  • Xu H, MJ Caimano, T Lin, M He, JD Radolf, SJ Norris, F Gheradini, AJ Wolfe, and XF Yang. 2010. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi. PLoS Pathog. 6:e1001104. PubMed
  • Tao Lin, Lihui Gao, Diane G. Edmondson, Mary B. Jacobs, Mario T. Philipp, and Steven J. Norris. 2009. Central Role of the Holliday Junction Helicase RuvAB in vlsE Recombination and Infectivity of Borrelia burgdorferi. PLoS Pathog 5: e1000679. doi:10.1371/doi:10.1371/ journal.ppat.1000679. PubMed
  • Nataliia Rudenko, Maryna Golovchenko, Tao Lin, Lihui Gao, Libor Grubhoffer, and James H Oliver Jr. 2009. Delineation of a new species of the Borrelia burgdorferi sensu lato complex, Borrelia americana sp.nov. J. Clin. Microbiol. 47 (12):3875–3880. PubMed
  • Liu J., T. Lin, D. J. Botkin, E. McCrum, H. Winkler, and S. J. Norris. 2009. Intact Flagellar Motor of Borrelia burgdorferi Revealed by Cryo-Electron Tomography: Evidence for Stator Ring Curvature and Rotor/C Ring Assembly Flexion. J. Bacteriol. 191(16):5026-5036. PubMed
  • James H. Oliver, Jr, Lihui Gao, and Tao Lin. 2008. Comparison of the spirochete Borrelia burgdorferi s. l. isolated from the tick Ixodes scapularis in southeastern and northeastern United States. J. Parasitol.26:1-6. PubMed
  • Lin, T., L. H. Gao, A. Seyfang, and J. H. Oliver, Jr. 2005. Candidatus Borrelia texasensis sp. nov. from the American dog tick, Dermacentor variabilis. Int. J. Syst. Evol. Microbiol. 55:685-693. PubMed
  • Lin, T., J. H. Oliver, Jr., and L. H. Gao. 2004. Molecular characterization of Borrelia isolates from ticks and mammals from the southern United States. J. Parasitol. 90:1298-1307. PubMed
  • Regassa, LB, KM Steward, AC Murphy, FF French, T Lin, and RF Whitecomb. 2004. Differentiation of group VIII Spiroplasma strains with sequences of the 16S-23S rDNA intergenic spacer region. Can. J. Microbiol. 50:1061-1067. PubMed
  • Oliver, J. H., Jr., T. Lin, L. Gao, K. L. Clark, C. W. Banks, L. A. Durden, A. M. James, and F. W. Chandler, Jr. 2003. An enzootic transmission cycle of Lyme borreliosis spirochetes in the southeastern United States. Proc. Natl. Acad. Sci. U.S.A. 100 (20): 11642-11645. The paper was accompanied by a News from PNAS “Lyme disease also permeates southern united states” PNAS News Archive091503. PubMed
  • Lin, T., J. H. Oliver, Jr., and L. Gao. 2003. Comparative analysis of Borrelia isolates from southeastern USA based on randomly amplified polymorphic DNA fingerprint and 16S ribosomal gene sequence analyses. FEMS Microbiol. Lett. 228: 249-257. PubMed
  • Lin, T., J. H. Oliver, Jr., and L. H. Gao. 2002. Genetic diversity of the outer surface protein C gene of southern Borrelia isolates and its possible epidemiological, clinical, and pathogenetic implications. J. Clin. Microbiol. 40: 2572-2583. PubMed
  • Lin, T., J. H. Oliver, Jr., and L. H. Gao. 2001. Genetic heterogeneity of Borrelia burgdorferi sensu lato in southern United States based on restriction fragment length polymorphism and sequence analysis. J. Clin. Microbiol. 39: 2500-2507. PubMed
  • Oliver, J. H. Jr., K. L. Clark, F. W. Chandler, Jr., T. Lin, A. M. James, C. W. Banks, L. O.Huey, A. R. Banks, D. C. Williams, and L. A. Durden. 2000. Isolation, cultivation, and characterization of Borrelia burgdorferi from rodents and ticks in the Charleston area of South Carolina. J. Clin. Microbiol. 38: 120-124. PubMed

Additional Information

Postdoctoral Research Fellow Position in Bacterial Pathogenesis and Host-Pathogen interactions

I am seeking a highly motivated postdoctoral research fellow to join our research project. The postdoctoral research fellow is going to characterize B. burgdorferi virulence determinants utilizing molecular approaches, including but not limited to genetic inactivation, complementation, functional characterization, and the mammalian and tick infection model.

The candidate should hold a PhD or equivalent degree in microbiology, immunology or other related fields and exhibit strong laboratory and analytical skills. Experience in bacteria pathogenesis/molecular biology/biochemistry is preferred.

The successful applicant will be working in an active research department within the renowned Texas Medical Center (TMC). To apply, please email a cover letter, CV, and names and contact information of three referees to Dr. Tao Lin at Tao.Lin@uth.tmc.edu.

Academic Appointments

Institute of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine

Institute for Communicable Disease Control and Prevention, Chinese Centers for Disease Control and Prevention

  • Assistant Professor, 1989‑1996.
  • Associate Professor, 1996-1997.

James H. Oliver, Jr. Institute of Arthropodology and Parasitology, America Tick Collection, Georgia Southern University

  • Research Scientist, 1999-2005.

Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School at Houston

  • Assistant Professor, 2005-2012.
  • Associate Professor, 2012-.

MD Anderson Cancer Center UT Health Graduate School of Biological Sciences at Houston

  • Assistant Professor, 2005-2012.
  • Associate Professor, 2012-.

Honors and Awards

  • Texas Higher Education Coordinating Board Norman Hackerman Advanced Research Program  Award, 2008
  • President’s Prize, Entomological Society of America, 1999.

Other Professional Activities

  • Associate Editor, Editorial Board, PLoS Neglected Tropical Diseases, 2016-.
  • Editor, Editorial Board, Frontiers in Cellular and Infection Microbiology, 2016-.
  • Editor, Editorial Board, Journal of Clinical & Experimental Pathology, 2011-.

Research Support

Active:

R21 AI111317-01, NIH, Linden Hu, Tao Lin, MPI, “Role of carbon availability in environmental adaptation by Borrelia burgdorferi”. 09/01/14-08/31/16.

R21 AI119572-01, NIH, Tao Lin, John M. Leong, MPI, “CRASP-mediated Serum Resistance by Borrelia burgdorferi”. 07/01/15-06/30/17.

2R01AI059048-09, NIH, Steven Norris, PI, Tao Lin Co-I, “Virulence Determinants of Borrelia burgdorferi”. 08/01/2013-07/31/2017.

R01AI121401-01, NIH, Jenifer Coburn, John Leong, MPI, Tao Lin Co-I, “Multiple B. burgdorferi Factors Collaborate to Evade Complement-Mediated Defenses”. 10/01/15-09/30/20

R21AI123672, NIH, Jonathan Skare, Jennifer Hyde, Meghan Lybecker, co-PI, Tao Lin, co-I, “The role of small non-coding RNA in borrelial pathogenesis”. 04/01/16-03/31/18.

Completed

Norman Hackerman Advanced Research Program Grant 011618-0016-2007, Texas Higher Education Coordinating Board, Tao Lin, PI, Steven Norris, Co-I, “Unraveling the Mystery of Lyme Disease and Southern Tick-Associated Rash Illness (STARI) in Texas”. 5/15/08-5/14/11

R21 AI103905-01, NIH, Linden Hu, Tao Lin, MPI, “Use of massively parallel sequencing for identification of B. burgdorferi virulence genes”. 09/01/13-08/31/16.

Media

  • UT Medical School Researchers to Study Lyme-Like Illness (Distinctions, May, 2007)
  • Scientists Step Up Hunt for Bacterial Genes Tied to Lyme Disease (Inside of UTHealth, November 05, 2012)