CIHR-UBC Strategic Training Program for Translational Research in Infectious Diseases Address: D452 – 2733 Heather Pavilion, Vancouver, BC V5Z 3J5 E-mail: tonychow@interchange.ubc.ca Voice: (604) 875-5063 Fax: (604) 875-4013 Website: http://cmdr.ubc.ca/trainingprogram Research Theme: Molecular pathogenesis, innate immunity, cell signalling, immunomodulation Sub-theme: Immunobiology of Chlamydia trachomatis Principal Investigator: Dr. R.C. Brunham, MD Telephone: Fax: E-mail: 604-660-1840 604-660-6066 robert.brunham@bccdc.ca We are using a systems biology approach to elucidate the interaction of the intracellular microbe, Chlamydia trachomatis with its host in order to develop a vaccine to prevent infection in humans. Systems biology is an inherently integrative and transdisciplinary approach to research that is based on the concept that living organisms are composed of complex interacting molecular and cellular networks and which exist within complex networks as interacting individuals. The application of a systems biology approach to research allows for the identification of key regulatory points in a system thereby allowing for both prediction and control. In the context of C. trachomatis we are using genomic and computational approaches to identify critical antigenic proteins in the organism that trigger protective T lymphocyte responses in the host and are focussing on membrane encoded proteins and proteins secreted via the type III secretion system. The antigenic proteins and/or their encoding nucleic acids are used as vaccines in ways that target host dendritic cell maturation and presentation of antigen to T cells and B-lymphocytes in the mucosal environment. We believe that a systems analytical approach to C. trachomatis immunobiology can result in the rational design of a Chlamydia vaccine and shed light on how to approach vaccine development for other intracellular pathogens of public health importance. Read TD, Brunham RC, Shen C, Gill SR, Heidelberg JF, White O, Hickey EK, Peterson J, Utterback T, Berry K, Bass S, Linher K, Weidman J, Khouri H, Craven B, Bowman C, Dodson R, Gwinn M, Nelson W, DeBoy R, Kolonay J, McClarty G, Salzberg SL, Eisen J, Fraser CM. Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 2000 Mar 15;28(6):1397-406. Dong-Ji Z, Yang X, Shen C, Lu H, Murdin A, Brunham RC. Priming with Chlamydia trachomatis major outer membrane protein (MOMP) DNA followed by MOMP ISCOM boosting enhances protection and is associated with increased immunoglobulin A and Th1 cellular immune responses. Infect Immun. 2000 Jun;68(6):3074-8. Brunham RC, Zhang DJ, Yang X, McClarty GM. The potential for vaccine development against chlamydial infection and disease. J Infect Dis. 2000 Jun;181 Suppl 3:S538-43. Review. Lu H, Shen C, Brunham RC. Chlamydia trachomatis infection of epithelial cells induces the activation of caspase-1 and release of mature IL-18. J Immunol. 2000 Aug 1;165(3):1463-9. Brinkham FSL, Blanchard JL, Cherkasov A, Av-Gay Y, Brunham RC, Fernandez RC, Finlay BB, Otto SP, Ouellette BFF, Keeling PJ, Rose AM, Hancock REW, Jones SJM. Evidence that plant-like genes in Chlamydia species reflect an ancestral relationship between Chlamydiaceae, Cyanobacteria, and the chloroplast. Genome Res. 2002;12 1159-1167 Lu H, Xing Z, Brunham RC. GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis. J Immunol 2002 December 1; 169(11):632431. Updated: August 2003 Page 1