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Regional Centers of Excellence Academic defense against bioterrorism

Regional Centers of Excellence Academic defense against bioterrorism. Great Lakes (Region V) RCE Illinois, Indiana, Michigan, Minnesota, Ohio & Wisconsin Director: Olaf Schneewind, University of Chicago. Argonne National Laboratory Battelle Memorial Institute IIT-Research Institute

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Regional Centers of Excellence Academic defense against bioterrorism

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  1. Regional Centers of ExcellenceAcademic defense against bioterrorism

  2. Great Lakes (Region V) RCEIllinois, Indiana, Michigan, Minnesota, Ohio & WisconsinDirector: Olaf Schneewind, University of Chicago Argonne National Laboratory Battelle Memorial Institute IIT-Research Institute Illinois Institute of Technology Illinois State University Loyola University Chicago Mayo Clinic Medical College of Wisconsin Michigan State University National Wildlife Health Center Northwestern University Ohio State University Purdue University University of Chicago University of Cincinnati University of Illinois University of Michigan University of Minnesota University of Notre Dame University of Toledo University of Wisconsin Wayne State University Wright State University

  3. Infectious Disease and Biodefense Research Frontiers

  4. Disease Agents Plague Yersinia pestis Anthrax Bacillus anthracis Smallpox Variola major Hemorrhagic Fever Ebola or Marburg Virus Tularemia Francisella tularensis Botulism Clostridium botulinum BioterrorismWhat are the major threats?

  5. RCE Products: At the Frontier of Biodefense • Vaccines: • Plague, Smallpox, Anthrax, Tularemia, Botulism, Ebola • Drugs: • Antibiotics, Antiinfectives, Disinfectants • Diagnostics

  6. UofC’s Ricketts Laboratory at ANL • Scheduled for completion in 2008 • BSL-3 facility • 45,000 sqf • Located at Argonne National Laboratory

  7. Smallpox • Causative agent Variola major • Clinical diagnosis • Also - Electron microscopy, antibody and DNA tests • Prevention: Vaccination • Therapy: Vaccination • Immunglobin, Cidofovir?

  8. Variola major

  9. Smallpox Pathogenesis

  10. Dark WinterSmallpox Attack Simulation (12/9-22/2002)

  11. Dark WinterNew Smallpox Cases Per Day

  12. Dark Winter - Summary

  13. VaccinationA scientific triumph

  14. Adverse Effect of VaccinationAtopic dermatitis and immune suppression

  15. Variola Genome

  16. Monkey pox in humans

  17. Smallpox research goals • Improved, attenuated vaccine • Drugs with proven efficacy • Real time detection • Evolution of poxviruses

  18. Incidence of Plague

  19. Plague • Causative agent: Yersinia pestis • Inhalational uptake or flea transmission • Clinical diagnosis (2-5 days) • Prevention: antimicrobials • Therapy: aminoglycoside

  20. Pneumonic Plague

  21. TOPOFF

  22. Pathogenic Elements of Plague

  23. Immune Modulatory Strategies of Y. pestis

  24. Y. pestis Type III Injection of Immune Cells

  25. LcrV at the Tip of Type III Needles Mueller et al. Science (2005)

  26. Yersinia pestis LcrVKey to Plague Vaccine and Immune Suppression Overheim et al. IAI (2005)

  27. rV10 Protection against Pneumonic Plaguei.n. challenge with 2,750 MLD Y. pestis CO92 DeBord et al. submitted (2006)

  28. B. anthracis Life style of a cheater

  29. AnthraxWhat goes around, comes around

  30. B. anthracisInvasion of macrophages

  31. Anthrax toxin pathogenesis

  32. Cutaneous anthrax lesion

  33. Anthrax as a weapon • Dissemination of infectious spores • Inhalational anthrax - lethal iwithin 48 hours • B. anthracis strains resistant to all antibiotics • Evasion of protective immunity?

  34. Sverdlovsk accident

  35. Research goals for anthrax • Vaccine that protects against respiratory anthrax • Drugs that inhibit antibiotic-resistant anthrax • Detection of anthrax spores in real time • Intelligence on engineered anthrax strains

  36. Botulism • Neurotoxin of Clostridium botulinum • Toxin uptake oral or respiratory • Clinical diagnosis - paralysis • Prevention - none • Therapy - none

  37. Botulinum neurotoxins (A-G)

  38. Pathogenesis of botulism

  39. Pathogenesis of botulism II

  40. Research goals for botulism • Vaccine development • Drugs that inactivate intracellular toxin • Real time detection

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