NERCE / BEID New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research

NERCE / BEID NIAID Strategic Plan –Category A, B, and C Priority Pathogens –Biology of the Microbe –Host Response – Diagnostics –Vaccines –Therapeutics – Research Resources »Regional Centers of Excellence »National Biocontainment Laboratories »Regional Biocontainment Laboratories

NERCE / BEID NIAID Priority Pathogens Category A  Bacillus anthracis (anthrax)  Clostridium botulinum  Yersinia pestis  Variola major (smallpox)  Francisella tularensis (tularemia)  Viral hemorrhagic fevers  Arenaviruses  Bunyaviruses  Hantaviruses  Rift Valley Fever  Flaviruses  Dengue  Filoviruses  Ebola  Marburg Category B  Burkholderia pseudomallei  Coxiella burnetti (Q fever)  Brucella species (brucellosis)  Ricin toxin (from Ricinus communis)  Epsilon toxin of Clostridium perfringens  Staphylococcus enterotoxin B  Typhus fever (Rickettsia prowazekii)  Food and Waterborne Pathogens  Bacteria  Diarrheagenic E.coli  Vibrio cholera  Salmonella  Viruses (Caliciviruses, Hepatitis A)  Protozoa  Cryptosporidium parvum  Additional viral encephalitides  West Nile Virus  EEE

NERCE / BEID Academic / Industry Partnership

NERCE / BEID New England Regional Center of Excellence All medical schools in New England contribute to governance and strategic planning Institutions currently with active major research projects: –Boston University Medical Center –Center for Blood Research –Harvard Medical School –University of Massachusetts – Dartmouth –University of Massachusetts Medical School –Brigham and Woman’s Hospital –Dartmouth Medical School

NERCE Strategic Plan -NERCE will provide the nation, as quickly and efficiently as possible, with vaccine and therapeutic interventions against infections caused by organisms used as weapons of bioterrorism -NERCE is using a genomics, proteomics, and high-throughput approach to biodefense development

NERCE / BEID NERCE Components 6 Research Programs 5 Developmental Projects Program 4 Core Laboratories / Programs 2 Career Development Programs Emergency Response Plan Regional and National Governance Committees

NERCE / BEID NERCE Research Programs Multiple Approaches to Blocking Toxin Action –Direct Inhibition of Anthrax Toxin Action John Collier, PI –Direct Blocking of Botulinium Toxin Action Bal Ram Singh, PI –Disruption by Small Molecules of Intracellular Toxin Transport Tomas Kirchhausen, PI –Mechanism(s) of Endocytic Vesicle Membrane Translocation by Diptheria Toxin, Anthrax Toxin, and Botulinium Neurotoxins Jack Murphy, PI

NERCE / BEID NERCE Research Programs Mediators and Inhibitors of Immunity to Yersinia pestis Michael Starnbach and John Goguen, PIs Microbial Vectors for Antigen Delivery John Mekalanos, David Knipe, and Darren Higgins, PIs Development of a Conjugate Vaccine for the Prevention of Tularemia Arthur Tzianabos and Dennis Kasper, PIs

NERCE / BEID NERCE Research Programs Discovery of Small Molecules to Block Fusion by Envelope Proteins of Dengue and Ebola Viruses Stephen Harrison, PI Innate Immunity to Hemorrhagic Fever Viruses Robert Finberg and Douglas Golenbock, PIs

NERCE / BEID NERCE Developmental Projects Studies of the SARS Receptor ACE2 Michael R. Frazan, PI Structure of Anthrax Spore Polysaccharide Julia Wang, PI SARS Coronavirus Pathogenesis in African Green Monkeys Keith G. Mansfield, PI Development of a Multi-gene Subunit-based smallpox vaccine Shan Lu, PI Novel Ways to Optimize CTL Response to Vaccinia Virus William R. Green, PI

NERCE / BEID NERCE Core Laboratories BSL-3 Animal and Tissue Culture Andrew Onderdonk, PI Proteomics Leonardo Brizuela, PI Harvard Institute of Proteomics Small Molecule Screening Steven Lory, PI Institute for Chemistry and Cell Biology Clinical Studies Raphael Dolin, PI

NERCE / BEID Career Development Program RFP Issued October 14 Applications due December 1 Funding Start March 1

NERCE / BEID Emergency Response Plan Provide facilities and scientific support to first- line responders in the event of a biodefense or naturally occurring biological emergency –Independent local confirmatory testing of a positive test result derived from Project BioWatch –Scientific expert resource –Laboratory testing consulting services, auxiliary sample testing, and sample storage and archiving

NERCE / BEID Regional Centers of Excellence Duke University Harvard Medical School New York State Department of Health University of Chicago University of Maryland University of Texas Medical Branch University of Washington Washington University in St. Louis

NBLs and RBLs National Biocontainment Laboratories –Boston University –University of Texas Medical Branch Regional Biocontainment Laboratories –Colorado State University –Duke University –Tulane University –University of Alabama at Birmingham –University of Chicago –University of Medicine and Dentistry of New Jersey –University of Missouri –University of Pittsburgh –University of Tennessee

NERCE / BEID Assembly and Action of Anthrax Toxin

NERCE / BEID Screening for chemicals that protect cells from anthrax toxin Cell Viability