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Lawrence Bergman

Professor

  • Department: Microbiology and Immunology
  • Research interests:  Malaria, invasion, global gene expression, merozoite, sporozoite, actin-myosin, microarray, Plasmodium
  • Education: 1979, University of Virginia, Charlottesville, Va.
  • Research Staff: Tom Daly 
  • Graduate Students: Kasturi Chatterjee, Sumit Kumar
Research

Malaria is the most common and deadly parasitic disease in the world. A number of factors have contributed to making malaria as serious a problem now as it was during the first half of the twentieth century. In any given year, there will be 300-500 million cases of malaria and 1-3% of those who contract the disease will not survive. Over 90% of the cases and deaths occur in Africa. As bad as that is, some experts foresee as much as a 20% annual increase in Africa's rate of malaria-related illness and death. Each year the world over, malaria destroys, through premature death and disability, the equivalent of at least 35 million years of healthy, productive human life and to date, there is no effective subunit vaccine for malaria. The incidence of drug-resistant parasite is increasing worldwide. The sequencing of the Plasmodium falciparum (and Plasmodium yoelii), the Anopheles gambiae and the Homo sapiens (and Mus musculus) genomes, the three organisms that comprise the complex life cycle of the malaria parasite, is complete and will aid in the study of the complex interactions responsible for the disease. Our laboratory is undertaking the investigation of two diverse topics, the protein-protein interactions involved in the invasion pathway and the whole genome expression analysis of various stages of the parasite life cycle, to potentially identify new targets for immunologic or chemotherapeutic intervention.

The invasive stages of apicomplexan parasites actively penetrate host cells, an essential ability for maintaining an intracellular lifestyle. What has become clear is that numerous parasite and host cell components participate in the rapid invasion process. The process of parasite invasion also involves a unique actin-myosin based motor that is localized between the plasma membrane and the inner membrane complex, a structure formed by two closely aligned membranes and supported by microtubules. Transmembrane proteins displaying adhesive properties were predicted to link the extracellular substrates with the motor. Studies are underway to analyze the proposed merozoite specific parasite ligand that links the red blood cell being invaded to the parasite actin-myosin motor. Again, using the yeast two-hybrid system and a bioinformatic approach we have identified components that link the actin-myosin motor to the inner membrane complex and may form one of the junctions involved in linking the parasite to the RBC to be invaded. Using structural information of the myosin-myosin light chain complex, we have potentially identified small molecule inhibitors of the invasion process. These studies have further led us to initiate the characterization of a second unique parasite myosin motor and its role in the life cycle of the parasite.

The second major aspect of the work in the laboratory involves the use of long-oligonucleotide gene-specific microarray to examine global patterns of gene expression in various stages of the rodent malaria P. yoelii. We have begun to characterize several potential nucleic acid binding proteins and the effects of over-expression or depletion on the global pattern of gene expression in the parasite.

Selected Publications:
  1. Bergman, L. W., Fujioka, H., Daly, T. M., Fox, S., Matuschewski, K., Nussenzweig, V., and S.H.I. Kappe. Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites, J. Cell Sci., 116: 39-49, 2003.
  2. Kappe, S. H. I., Buscaglia, C. A., Bergman, L. W., Coppens, I., and V. Nussenzweig. Apicomplexan gliding motility and host cell invasion: overhauling the motor model. Trends in Parasitology, 20: 13-16, 2004.
  3. Mello, K., Daly, T. M., Long, C. A., Burns, J. M., and L. W. Bergman. MSP-7 family members with similar expression patterns differ in ability to immunize against Plasmodium yoelii malaria. Infection and Immunity, 72: 1010-1018, 2004.
  4. Li, X., Chen, H., Oo, T. H., Daly, T. M., Bergman L. W., Chishti, A. H., and S. S. Oh. A co-ligand complex anchors Plasmodium falciparum merozoites to the erythrocyte invasion receptor band 3. J. Biol. Chem., 279: 5765-5771, 2004.
  5. Waters N. C., Knight, J. P., Creasy, C. L., and L. W. Bergman. The yeast Pho80-Pho85 cyclin-CDK complex has multiple substrates. Curr. Genet., 46: 1-9, 2004.
  6. Knight, J. P., Daly, T. M., and L. W. Bergman. Regulation by phosphorylation of Pho81p, a cyclin-dependent kinase inhibitor in Saccharomyces cerevisiae. Curr. Genet., 46: 10-19, 2004.
  7. Germann, M., Swain, E., Bergman, L. W. and J. T. Nickels, Jr. Characterizing the sphingolipid signaling pathway that remediates defects associated with loss of the yeast amphiphysin-like orthologs, Rvs161p and Rvs167p. J. Biol. Chem., 280: 4270-4278, 2005.
  8. Shi, Q., Cernetich, A. Daly, T. M., Galvin, G., Vaidya, A. B., Bergman, L. W. and J. M. Burns. Alteration in host cell tropism limits the efficacy of immunization with a surface protein of malaria parasites. Infection & Immunity, 73: 6363-6371, 2005.
  9. Bosch, J., Turley, S., Daly, T. M., Bogh, S. M., Villasmil, M. L., Zhou, N., Morrisey, J. M., Vaidya, A. B., Bergman, L. W. and W. G. J. Hol. Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proc. Natl. Acad. Sci. USA, 103: 4852-4857, 2006.
  10. Bosch, J., Turley, S., Roach, C. M., Daly, T. M., Bergman, L. W. and W. G. J. Hol. The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery. J Mol Biol., 372: 77-88, 2007.
  11. Tarun, A. S., Peng, X., Dumpit, R. F., Ogata, Y., Silva-Rivera, H., Camargo, N. Daly, T. M., Bergman, L. W. and S. H. Kappe. A combined transcriptome and proteome survey of malaria parasite liver stages. Proc. Natl. Acad. Sci. USA, 105: 305-310, 2008.
  12. Mikolajczak, S. A., Silva-Rivera, H., Peng, X., Tarun, A. S., Camargo, N., Jacobs-Lorena, V., Daly, T. M., Bergman, L. W., de la Vega, P., Williams, J., Aly, A. S. and S. H. Kappe. Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host. Mol Cell Biol., 28: 6196-6207, 2008.
  13. Magrini, K. D., Basu, A., Spotila, J. R., Avery, H. W., Bergman, L. W., Hammond, R. and S. Anandan. DNA microarrays detect effects of soil contamination on Arabidopsis thaliana gene expression. Environ. Toxicol. Chem., 27: 2476-2487, 2008.
  14. Heiss, K., Nie, H., Kumar, S., Daly, T. M., Bergman, L. W. and K. Matuschewski. Functional characterization of a redundant Plasmodium TRAP family invasin, TRAP-like protein, by aldolase binding and a genetic complementation test. Eukaryot. Cell., 7: 1062-1070, 2008.
  15. Gissot, M., Ting, L. M., Daly, T. M., Bergman, L. W. and P. Sinnis. High mobility group protein HMGB2 is a critical regulator of plasmodium oocyst development. J. Biol. Chem., 283: 17030-17038, 2008.
 

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